MedWorm.com provides a medical RSS filtering service. Over 6000 RSS medical sources are combined and output via different filters. This feed contains the latest items from the 'Archiv der Pharmazie' source. Wed, 08 Feb 2012 14:03:59 +0100 http://www.medworm.com/index.php?rid=5659930&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100204 AbstractA new class of biologically active 13‐membered phosphorus‐macroheterocycles (6a–l) were conveniently synthesized from 1,2‐bis(salicylidene amino)‐phenylene (1), by treating with phosporusoxychloride (3) and followed by reacting with various aromatic thiols and amines (5f–l) in one path, and in another path 1 was directly treated with various phosphorodichloridates (2a–e) in the presence of triethylamine at 0–10°C under N2 atmosphere in THF. All the title compounds were confirmed by analytical and spectral data (IR, 1H‐, 13C‐, 31P‐NMR, and mass spectra) and screened for anti‐oxidant activity. Among these compounds, 6k, 6e, and 6l containing nitro, fluoro, and chloro groups as substituents on the phenyl ring exhibited high anti‐oxidant activity with effecti... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5659930 Fri, 03 Feb 2012 05:00:00 +0100 5659930 http://www.medworm.com/index.php?rid=5659929&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100333 AbstractA series of novel compounds were synthesized in reactions of N3‐substituted amidrazones with cis‐1,2‐cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. All new structures were confirmed by H1 NMR and IR spectrometry as well as elemental analysis. Potential biological effects of new compounds were predicted with the Prediction of Activity Spectra for Substances (PASS) program. Antiviral, antibacterial, analgesic, and anti‐inflammatory activities were experimentally verified.A series of novel compounds were synthesized in reactions of N3‐substituted amidrazones with cis‐1,2‐cyclohexanedicarboxylic anhydride: linear, isoindole, and triazole derivatives. The potential biological effects of the new compounds were predicted with the PASS program... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5659929 Fri, 03 Feb 2012 05:00:00 +0100 5659929 http://www.medworm.com/index.php?rid=5659928&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100373 Abstract3‐Bromo‐4,5‐bis(2,3‐dibromo‐4,5‐dihydroxybenzyl)‐1,2‐benzenediol (BDB) is a bromophenol purified from the marine red alga Rhodomela confervoides and exhibits potent protein tyrosine phosphatase 1B (PTP1B) inhibition (IC50 = 1.7 µmol/L). In an effort to improve the PTP1B inhibitory activity, a series of derivatives were designed, synthesized, and evaluated in vitro. The preliminary structure–activity relationship indicated that the tricyclic scaffold and multi‐bromine atoms (four to five) attached to the aryl rings are important for PTP1B inhibition. Among these, compound 26 exhibited remarkable inhibitory activity against PTP1B with an IC50 of 0.89 µmol/L, which was approximately two‐fold more potent than the initial lead compound BDB.A series of bro... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5659928 Wed, 01 Feb 2012 05:00:00 +0100 5659928 http://www.medworm.com/index.php?rid=5620273&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201290001 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5620273 Mon, 23 Jan 2012 18:32:33 +0100 5620273 http://www.medworm.com/index.php?rid=5609094&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100225 AbstractA new series of N‐(benzoylphenyl) and N‐(acetylphenyl)‐1‐benzofuran‐2‐carboxamides (3a–3d and 4a′–4c′) were synthesized. Compounds (3a, 3b, and 4a′–4c′) were tested in vivo using Triton‐WR‐1339‐induced hyperlipidemic rats as an experimental model for their hypolipidemic activity. The tested animals were divided into eight groups: control, hyperlipidemic, 3a, 3b, 4a′, 4b′, 4c′, and bezafibrate. At a dose of 15 mg/kg, the elevated plasma triglyceride (TG) levels were significantly reduced in compounds 3b (p <0.0001) and 4c′ (p <0.05) after 12 and 24 h compared to the normal control group. Furthermore, high‐density lipoprotein‐cholesterol levels were remarkably increased in compounds 3b (p <0.001) and 4c′ (p <0.05).... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5609094 Fri, 20 Jan 2012 05:00:00 +0100 5609094 http://www.medworm.com/index.php?rid=5609093&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100379 AbstractA new series of 3‐hydroxy‐8‐nitroimidazo[5,1‐b]‐1,4,5,6‐tetrahydropyrimidine systems, being potential tuberculostatic agents, were synthesized. These products are close structural analogs of the basic structure of the known antitubercular bicyclic nitroimidazooxazine PA‐824. The structures of the products obtained were confirmed by X‐ray methods on the example of 3‐hydroxy‐8‐nitro‐1‐phenylaminoimidazo[5,1‐b]‐1,4,5,6‐tetrahydropyrimidine. Evaluation of these products for their anti‐tuberculosis effects revealed interesting structure–activity relationships.A new series of 3‐hydroxy‐8‐nitroimidazo[5,1‐b]‐1,4,5,6‐tetrahydropyrimidine systems were synthesized. These products are close structural analogs of the basic structure of the antitu... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5609093 Fri, 20 Jan 2012 05:00:00 +0100 5609093 http://www.medworm.com/index.php?rid=5609092&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100377 AbstractIn order to increase the intestinal permeability of valsartan, 14 esters and peptide derivatives of valsartan were chemically synthesized and their absorption characteristics were described. All derivatives were stable and could be better absorbed into the small intestine than valsartan. There are two barriers for the absorption of valsartan derivatives. The elongated half‐life (t1/2) and stable blood concentrations for compound 4 due to the hydrolysis of the ester group in the second barrier were demonstrated in pharmacokinetic experiments. Furthermore, compound 4 also displayed modest anti‐hypertension activity in vivo, which makes structural modification of valsartan, especially for the purpose of improvement of its intestinal permeability, valuable for further studies.Fourt... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5609092 Fri, 20 Jan 2012 05:00:00 +0100 5609092 http://www.medworm.com/index.php?rid=5560363&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100064 AbstractA new series of 2,5‐diaryliminothiazolidin‐4‐ones were designed and synthesized as potent antiproliferative agents. The antiproliferative activities of the 25 target compounds were evaluated against three cancer cell lines (A549, H460 and HT29) by MTT assay. Pharmacological data indicated that most of the compounds possessed moderate activity, some showed remarkable activity against one or more cell lines. As the most promising compound, 8s (with IC50 values of 1.1, 0.01 and 1.3 µM against the A549, H460 and HT29 cell lines) was 1.1‐ to 270‐fold more potent than the reference drug sorafenib. Furthermore, preliminary structure–activity relationships (SARs) were summarized to provide guidance for further design and discovery of 2‐iminothiazolidin‐4‐one‐based an... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5560363 Mon, 02 Jan 2012 05:00:00 +0100 5560363 http://www.medworm.com/index.php?rid=5609091&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100345 AbstractA new series of 4‐aryl‐4H‐chromenes bearing a 5‐arylisoxazol‐3‐yl moiety at the C‐4 position were prepared as potential anticancer agents. The in vitro cytotoxic activity of the synthesized compounds was investigated against a panel of tumor cell lines including MCF‐7 (breast cancer), KB (nasopharyngeal epidermoid carcinoma), Hep‐G2 (liver carcinoma), MDA‐MB‐231 (breast cancer), and SKNMC (human neuroblastoma) using the MTT colorimetric assay. Doxorubicin, a well‐known anticancer drug, was used as positive standard drug. Among the synthesized compounds, the 5‐(3‐methylphenyl)isoxazol‐3‐yl analog (7j) showed the most potent cytotoxic activity against all five human tumor cell lines.A series of 2‐amino‐3‐cyano‐4‐(5‐arylisoxazol‐3‐yl)‐... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5609091 Sun, 01 Jan 2012 05:00:00 +0100 5609091 http://www.medworm.com/index.php?rid=5582062&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000327 AbstractSeveral triterpenoic acids display a remarkable cytotoxicity on tumor cells. Glycyrrhetinic acid – the main content of the licorice root – possesses an apoptotic effect on tumor cells. Previous studies pointed out the presence of a keto group at position C‐11 in glycyrrhetinic acid derivatives as the main reason for its apoptotic activity. Several pairs of derivatives were synthesized differing only at position C‐11. These compounds were tested in a sulforhodamine B colorimetric assay for cytotoxicity screening on 12 tumor cell lines and mouse embryonic fibroblasts (NIH3T3). Our results show that there is no direct relation between the existence of the C‐11 keto group and the apoptotic activity of the compounds.It remains disputable whether the C11 keto group in glycyrrhe... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5582062 Sun, 01 Jan 2012 05:00:00 +0100 5582062 http://www.medworm.com/index.php?rid=5582061&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201290000 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5582061 Sun, 01 Jan 2012 05:00:00 +0100 5582061 http://www.medworm.com/index.php?rid=5524996&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100279 AbstractThe interaction between leukocytes and the vascular endothelial cells (EC) via cellular adhesion molecules plays an important role in the pathogenesis of various inflammatory and autoimmune diseases. Small molecules that block these interactions have been targeted as potential therapeutic agents against acute and chronic inflammatory diseases. In an effort to identify potent intercellular cell adhesion molecule‐1 (ICAM‐1) inhibitors, a large number of arylalkyl ketones, benzophenones, desoxybenzoins and chalcones and their analogs (54 in total) have been synthesized and screened for their ICAM‐1 inhibitory activity. The structure‐activity relationship studies of these compounds identified three potent chalcone derivatives and also demonstrated the possible mechanism for the... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5524996 Tue, 20 Dec 2011 05:00:00 +0100 5524996 http://www.medworm.com/index.php?rid=5487024&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100256 AbstractThe synthesis of a series of novel α‐aminosubstituted phosphonates was accomplished by the reaction of various substituted aldehydes with an amine amlodipine (3‐ethyl 5‐methyl (±)2‐((2‐aminoethoxy)methyl)‐4‐(2‐chlorophenyl)‐6‐methyl‐1,4‐dihydropyridene‐3,5‐dicarboxylate) followed by diethylphosphite/dibutylphosphite in ethanol using SnCl2.2H2O as a Lewis acid catalyst, under conventional and ultrasonic irradiation. Their structures were established by analytical and spectral data. The title compounds showed good antibacterial, antifungal and antiviral activity depending on the nature of the bioactive groups at the α‐carbon.A new class of α‐aminosubstituted phosphonates was synthesized and evaluated for their antimicrobial and antiviral activity. ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5487024 Wed, 07 Dec 2011 05:00:00 +0100 5487024 http://www.medworm.com/index.php?rid=5487023&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100309 AbstractAs part of our studies focused on the design and synthesis of new antimicrobial agents a series of 7‐fluoro‐3,4‐dihydro‐2H‐1,4‐benzothiazine derivatives (4a–4f, 4h) and 7‐fluoro‐2H‐1,4‐benzothiazin‐3(4H)‐one analogues (4j–4o) were synthesized and evaluated for their in vitro inhibitory activity against a representative panel of Gram‐positive and Gram‐negative bacteria strains and also toward selected fungi species. These compounds were prepared in one step from chloro‐substituted‐2‐amino‐5‐fluorobenzenethiol 6a–6c. The biological screening identified in compounds 4a, 4j and 4l the most promising results of both series showing an interesting antimicrobial activity. Our antibiotic investigation was also completed by testing the key intermed... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5487023 Wed, 07 Dec 2011 05:00:00 +0100 5487023 http://www.medworm.com/index.php?rid=5487022&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100272 In conclusion, the new compounds are promising molecules to be used owing to their potential antioxidant properties.(3,4‐Dihydroxyphenyl)(2,3,4‐trihydroxyphenyl)methanone (5) and its two derivatives with bromine were synthesized. 4‐(3,4‐Dihydroxybenzyl)benzene‐1,2,3‐triol and its dibromide derivative (16) were also synthesized. The in vitro antioxidant activities of nine new compounds were determined, showing that the synthesized bromophenols had effective antioxidant power. The phenol 5 with two phenolic rings and five phenolic hydroxyl groups was the most potent antioxidant and radical scavenger. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5487022 Wed, 07 Dec 2011 05:00:00 +0100 5487022 http://www.medworm.com/index.php?rid=5560362&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100352 AbstractThe synthesis and the antitumor activity and fluorescent properties screening of novel bisphosphonate conjugates with cytotoxic 3,5‐bis((hetero)arylidene)‐4‐piperidone residues were performed. The facile and rapid synthetic route was based on the aza‐Michael addition of NH‐3,5‐bis((hetero)arylidene)‐4‐piperidones to tetraethyl ethylidenebisphosphonate. The synthesized compounds displayed high inhibitory properties towards Caov3, A549, PC3, and KB 3‐1 human carcinoma cell lines. Among those, compounds bearing 4‐cyano‐phenyl and 3‐pyridinyl substituents were revealed as the most active drug candidates with IC50 values in the range of 0.5–2.5 µM. Methylenebisphosphonate with 4‐Me2N‐C6H4 groups in the piperidone framework possessing fluorescence propert... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5560362 Thu, 01 Dec 2011 05:00:00 +0100 5560362 http://www.medworm.com/index.php?rid=5524995&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100335 Abstract2‐Tosylacetonitrile (1) when reacted with α,β‐unsaturated nitriles 2a–c or a mixture of formaldehyde and 3‐amino‐2‐substituted‐pent‐2‐endinitriles 6a,b yielded pyridine derivatives 3a–c and 9a,b, respectively, while when subjected to react with salicylaldehyde yielded chromene derivatives 4 and 5, subsequently. The behavior of thiocarbamoyl derivative 10 derived from 1 towards some α‐halogenated compounds have been investigated as well as its behavior towards elemental sulfur and phenyl isothiocyanate. Newly synthesized compounds were screened for their antioxidant activity, erythrocytes haemolysis and bleomycin‐independent DNA damage. Some of the tested compounds exhibited promising activities.2‐Tosylacetonitrile (1) was reacted to pyridine derivatives... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5524995 Thu, 01 Dec 2011 05:00:00 +0100 5524995 http://www.medworm.com/index.php?rid=5487021&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100181 AbstractA new series of N,N′‐(benzene‐1,3‐diyldi‐1,3,4‐oxadiazole‐5,2‐diyl)bis{2‐[(5‐benzene‐1,3‐diyl‐1,3,4‐oxadiazol‐2‐yl)amino]acetamide}(macrocycle 1), N,N′‐(benzene‐1,3‐diyldi‐1,3,4‐thiadiazole‐5,2‐diyl)bis{2‐[(5‐benzene‐1,3‐diyl‐1,3,4‐thiadiazol‐2‐yl)amino]acetamide} (macrocycle 2) and S,S′‐[benzene‐1,3‐diylbis(4H‐1,2,4‐triazole‐5,3‐diyl)]bis{[(5‐benzene‐1,3‐diyl‐4H‐1,2,4‐triazol‐3‐yl)sulfanyl]ethanethioate}(macrocycle 3) was synthesized from isophthalic dihydrazide (4) through a multistep reaction sequence. All the synthesized compounds were screened for their inhibitory effect against four different bacterial strains: P. aeruginosa ATCC‐20852, K. pneumoniae MTCC‐618, S. aureus ATCC‐... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5487021 Thu, 01 Dec 2011 05:00:00 +0100 5487021 http://www.medworm.com/index.php?rid=5469106&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190011 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5469106 Thu, 01 Dec 2011 05:00:00 +0100 5469106 http://www.medworm.com/index.php?rid=5441206&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100170 AbstractThree series of novel 1,3,5‐trisubstituted 2‐pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized. The in vitro antitumor activity of the obtained compounds was determined at the National Cancer Institute (NCI). The 5‐(benzo[d][1,3]dioxol‐5‐yl)‐3‐(4‐methoxyphenyl)‐4,5‐dihydro‐1H‐pyrazole‐1‐carbothioamide (9a) is the most prominent of the compounds due to its remarkable activity toward leukemia (RPMI‐8226), renal cancer (UO‐31) and prostate cancer (DU‐145) cell lines with GI50 values of 1.88, 1.91 and 1.94 µM, respectively.Three series of novel 1,3,5‐trisubstituted 2‐pyrazoline derivatives containing thiophene and benzodioxol moieties as potential antitumor agents were synthesized... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5441206 Tue, 22 Nov 2011 05:00:00 +0100 5441206 http://www.medworm.com/index.php?rid=5400868&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000229 AbstractA novel series of aminopyrimidines containing the phenoxy isobutyric acid group as a pharmacophore was synthesized using conventional and microwave assisted methods of synthesis. The compounds were synthesized in good yields (70–89%) by the microwave‐assisted one‐pot protocol in much shorter reaction times. The synthesized compounds were evaluated for their hypolipidemic and hypoglycemic activity by high‐fat diet‐induced hyperlipidemia and hyperglycemia in male Sprague‐Dawley rats. The present investigation showed significant antihyperlipidemic and antihyperglycemic activity for all compounds of the series when compared with the standard drug. Structure‐activity relationship (SAR) for the series were developed by comparing total lipid profile data of synthesized compo... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5400868 Fri, 11 Nov 2011 05:00:00 +0100 5400868 http://www.medworm.com/index.php?rid=5400867&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000327 AbstractSeveral triterpenoic acids display a remarkable cytotoxicity on tumor cells. Glycyrrhetinic acid – the main content of the licorice root – possesses an apoptotic effect on tumor cells. Previous studies pointed out the presence of a keto group at position C‐11 in glycyrrhetinic acid derivatives as the main reason for its apoptotic activity. Several pairs of derivatives were synthesized differing only at position C‐11. These compounds were tested in a sulforhodamine B colorimetric assay for cytotoxicity screening on 12 tumor cell lines and mouse embryonic fibroblasts (NIH3T3). Our results show that there is no direct relation between the existence of the C‐11 keto group and the apoptotic activity of the compounds.It remains disputable whether the C11 keto group in glycyrrhe... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5400867 Fri, 11 Nov 2011 05:00:00 +0100 5400867 http://www.medworm.com/index.php?rid=5400866&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100138 AbstractA new group of regioisomeric 2,3‐diaryl‐1,3‐benzdiazinan‐4‐ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase‐2 (COX‐2) inhibitory activity. In vitro COX‐1/COX‐2 inhibition studies identified 3‐(p‐fluorophenyl)‐2‐(4‐methylsulfonylphenyl)‐1,3‐benzdiazinane‐4‐one (2b) as a potent and highly selective (IC50 = 0.07 µM; selectivity index = 572.8) COX‐2 inhibitor.A new group of regioisomeric 2,3‐diaryl‐1,3‐benzdiazinan‐4‐ones, possessing a methyl sulfonyl pharmacophore, were synthesized and their biological activities were tested for cyclooxygenase‐2 (COX‐2) inhibitory activity. In vitro COX‐1/COX‐2 inhibition studies identified 3‐(p‐fluoro... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5400866 Fri, 11 Nov 2011 05:00:00 +0100 5400866 http://www.medworm.com/index.php?rid=5387197&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100128 AbstractA series of 1‐(4‐methoxyphenyl)‐2‐[5‐{(biphenyl‐4‐yloxy)methyl}4‐(substituted phenyl)‐3‐mercapto‐(4H)‐1,2,4‐triazol‐3‐ylthio)] ethanones (6a–6s) and 4‐(substituted phenyl)‐3‐(morpholin/pyrrolidin‐4‐ylmethylthio)‐5‐(4‐phenylphenoxymethyl)‐4H‐1,2,4‐triazoles (7a–7e) were synthesized in order to obtain new compounds with potent anti‐inflammatory and analgesic activity with insignificant ulceration. Among the synthesized compounds, (6c), (6e), (6g) and (6l) from triazole series and (7b) and (7e) from Mannich base series were found to exhibit significant anti‐inflammatory activity with 59.69, 59.69, 64.69, 79.84, 54.54, 79.69% and 52.55, 57.50, 72.52, 83.03, 60.06, 84.08% inhibition of paw edema at 3 h and 5 h respectively,... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5387197 Wed, 02 Nov 2011 04:00:00 +0100 5387197 http://www.medworm.com/index.php?rid=5441205&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100203 AbstractA new series of pyrano[4,3‐b]pyran 4a–i and pyrano[3,2‐c]chromene 6a–r derivatives bearing a 2‐thiophenoxyquinoline nucleus were synthesized by reaction of 2‐(4‐(un)‐substituted thiophenoxy)quinoline‐3‐carbaldehydes 2a–i with 6‐methyl‐4‐hydroxypyran‐2‐one 3 and 4‐hydroxy‐6‐(un)‐substituted‐2H‐chromen‐2‐one 5a–b respectively and malononitrile at room temperature in the presence of KOH as a basic catalyst. All the compounds were screened against three Gram‐positive bacteria (Streptococcus pneumoniae, Bacillus subtilis, Clostridium tetani), three Gram‐negative bacteria (Salmonella typhi, Escherichia coli, Vibrio cholerae) and two fungi (Candida albicans, Aspergillus fumigatus) using the broth microdilution MIC (minimum inhibitory c... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5441205 Tue, 01 Nov 2011 04:00:00 +0100 5441205 http://www.medworm.com/index.php?rid=5408410&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100028 AbstractA high yielding three‐step procedure was applied for the synthesis of N‐(imidazolidin‐2‐ylidene)‐1‐arylmethanamine oxides 3 (α‐aminonitrones) starting from the easily accessible imidazolidin‐2‐one O‐benzyl oxime 1. The α‐aminonitrone–α‐iminohydroxyloamine tautomerism of these products was studied theoretically and the structures of the synthesised compounds were confirmed by single crystal X‐ray crystallographic analysis. The compounds were evaluated in vitro for their binding affinities to α1 and α2 adrenoceptors as well as imidazoline I1 and I2 receptors. The highest potencies at the α2 adrenergic receptors were observed for compounds bearing biphenyl (4h,Ki = 9 nM) and naphthyl (4i,Ki = 92 nM) moieties. Compounds 4h and 4i were further t... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5408410 Tue, 01 Nov 2011 04:00:00 +0100 5408410 http://www.medworm.com/index.php?rid=5400865&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100265 AbstractTwo divergent series of novel chalcone analogs, one derived from 1‐cyclohexylpyrrolidin‐2‐one and the other derived from 1‐benzo[f]chromanone, were designed, synthesized and evaluated for cytotoxicity against two murine cancer cell lines. Two 1‐benzo[f]chromanone analogs, 4g and 4j yielded moderate toxicity against both melanoma B16 and lymphoma L1210 cell lines with IC50 values between the range of 5 and 6 µM. With an IC50 value of 3.4 µM, compound 4g was also active against human MDA‐MB‐435 melanoma cells. X‐ray structures of the β‐hydroxy ketone product (4a) and the α,β‐unsaturated ketone (4h) were collected, and confirm the syn‐configuration between the carbonyl moiety and the β‐vinylic proton in 4h. X‐ray structures of two 1‐cyclohexylpyrr... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5400865 Tue, 01 Nov 2011 04:00:00 +0100 5400865 http://www.medworm.com/index.php?rid=5387196&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100186 AbstractThe versatile synthon (E)‐2‐((dimethyl amino)methylene)cyclooctanone (2) was used as a key intermediate for the synthesis of cyclooctanones and cyclooctane‐based heterocycles with pyrazole, isoxazole, pyrimidine, pyrazolopyrimidine, triazolopyrimidine and imidazopyrimidine derivatives via its reactions with several nitrogen nucleophiles. The newly synthesized compounds were screened in vitro for their antimicrobial activity against pathogenic microorganisms (Listeria monocytogenes, methicillin‐resistant Staphylococcus aureus (MRSA), Staphylococcus aureus, Pseudomonas aeruginosa and Candida albicans). Most of the tested compounds showed moderate to high antibacterial and antifungal effects against the tested pathogenic microorganisms. Among the synthesized compounds, 2‐((p... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5387196 Tue, 01 Nov 2011 04:00:00 +0100 5387196 http://www.medworm.com/index.php?rid=5360541&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190010 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5360541 Mon, 31 Oct 2011 05:25:27 +0100 5360541 http://www.medworm.com/index.php?rid=5360539&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100209 AbstractAlteration of the acetylation state of histone proteins contributes to transcriptional regulation and epigenetic inheritance. Dysregulation of these processes may lead to human diseases, especially cancer. One of the major chromatin modifications is histone acetylation and this review gives an overview of the role of histone acetyltransferases, their structural aspects, as well as of chemical modulators targeting their enzymatical activities. Inhibitors and activators of histone acetyltransferases are presented and their capability to influence histone and non‐histone protein acetylation levels is discussed. Development of small molecules as epigenetic tools that alter histone acetyltransferase activity will be helpful to better understand the consequences of histone and generall... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5360539 Mon, 31 Oct 2011 05:22:23 +0100 5360539 http://www.medworm.com/index.php?rid=5360540&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100104 AbstractA mild and versatile method for the synthesis of some novel indole‐1‐carbinols has been developed via one‐pot reaction of indoles and paraformaldehyde in the presence of an excess of CaO, MgO, ZnO or TiO2. The solvent‐free reaction provided all the indole derivatives in moderate to good yields and short reaction times. Moreover, the effect of some selected indole‐1‐carbinols on cell proliferation of the hepatoma cell line FaO was evaluated.In the present work, we propose a simple and solvent‐free protocol for the synthesis of novel indole‐1‐carbinols also studying their stability in acidic milieus. Some selected compounds showed an interesting apoptotic effect on FaO cells. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5360540 Fri, 28 Oct 2011 04:00:00 +0100 5360540 http://www.medworm.com/index.php?rid=5336077&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100124 AbstractIn the present study, some amide derivatives were synthesized and their potential anticholinesterase properties were investigated. N‐(Benzothiazol‐2‐yl)‐2‐[(5‐amino/methyl‐1,3,4‐thiadiazol‐2‐yl)thio]acetamide derivatives were obtained by nucleophilic substitution of 2‐chloro‐N‐(benzothiazole‐2‐yl)acetamide derivatives with appropriate 1,3,4‐thiadiazole‐2‐thioles. The chemical structures of the compounds were elucidated by 1H‐NMR, 13C‐NMR and FAB+‐MS spectral data and elemental analyses. Each amide derivative was evaluated for its ability to inhibit AChE and BuChE using a modification of Ellman's spectrophotometric method. The compounds were also investigated for their cytotoxic properties using MTT assay. 2‐(5‐Amino‐1,3,4‐thiadiazol... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5336077 Tue, 18 Oct 2011 04:00:00 +0100 5336077 http://www.medworm.com/index.php?rid=5336076&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100250 AbstractA new series of 1,4‐disubstituted phthalazinylpiperazine derivatives 7a–f, 12a–f and 20a–f were designed and synthesized in order to develop potent and selective antitumor agents. The target compounds were screened for their cytotoxic activities against A549, HT‐29 and MDA‐MB‐231 cancer cell lines in vitro. Among them, compounds 7a–f exhibited excellent selectivity for MDA‐MB‐231 with IC50 values ranging from 0.013 µM to 0.079 µM. The most promising compound, 7e (IC50 = 2.19 µM, 2.19 µM, 0.013 µM), was 9.3, 10, and 4.9 × 103 times more active than vatalanib (IC50 = 20.27 µM, 21.96 µM, 63.90 µM), respectively.A new series of 1,4‐disubstituted phthalazinylpiperazine derivatives 7a–f, 12a–f and 20a–f were designed and sy... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5336076 Tue, 18 Oct 2011 04:00:00 +0100 5336076 http://www.medworm.com/index.php?rid=5336075&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100047 AbstractStructural feature analysis of chlorogenic acid derivatives made up of varying lengths of alkyl groups as α‐glucosidases inhibitors were performed by QSAR techniques. The statistically significant models derived from the study were validated by leave one out, Y‐randomization and test set methods. The predictive capacity of the models was assessed by its validation parameters such as crossvalidated correlation coefficients (Q2), predictive residual analysis and other correlation parameters. The results obtained from the study show that the models were constructed with vsurf like properties (vsurf_ID4, vsurf_ID7 and vsurf_CW8), partial charge (Q_VSA_FNEG) and conformation dependent charged (dipoleX) descriptors. The integy moments of hydrophobicity descriptors (ID4 and ID7) are ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5336075 Tue, 18 Oct 2011 04:00:00 +0100 5336075 http://www.medworm.com/index.php?rid=5314714&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100046 In this study we varied glycyrrhetinic acid at position C‐30 to get “simple” derivatives, for example esters, amides and a nitrile. The influence of these changes on the cytotoxic activity is noteworthy and was determined by a colorimetric sulphorhodamine B test using 7 human tumor cell lines and mouse embryonic fibroblasts (NIH3T3) for comparison. A Trypan blue test as well as an acridine orange/ethidium bromide test was used to discover the ability of the compounds to induce apoptosis.Some esters of glycyrrhetinic acid show improved antitumor activity; they act by apoptosis. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314714 Fri, 14 Oct 2011 04:00:00 +0100 5314714 http://www.medworm.com/index.php?rid=5314712&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100065 AbstractArglabin derivatives varied at the endo‐ or exo‐cyclic double bond were synthesized and studied in a colorimetric sulforhodamine B assay for their cytotoxicity. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α‐methylene‐γ‐butyrolactone moiety led to compounds of similar or only slightly reduced cytotoxicity but different, cell line‐dependent selectivity. In addition, arglabin is an excellent starting material for the synthesis of the guaianolide arborescin.Arglabin derivatives varying at the endo‐ or exo‐cyclic double bond were synthesized. Variations on the endocyclic double bond led to compounds of reduced cytotoxicity whereas derivatives from the reaction of the α‐methylene‐γ�... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314712 Fri, 14 Oct 2011 04:00:00 +0100 5314712 http://www.medworm.com/index.php?rid=5314711&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100140 AbstractVarious 1‐[6‐(4‐substituted phenyl)‐3‐cyano‐4‐(substituted phenyl)‐pyridin‐2‐yl]‐5‐oxopyrrolidine‐3‐carboxylic acids (3a–t) were designed and synthesized by clubbing pyrrolidinones and pyridines, the two active anticonvulsant pharmacophores. All the synthesized compounds fulfilled the requirements of suggested pharmacophoric model for anticonvulsant activity. Their in vivo anticonvulsant evaluation was performed by maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) tests. The minimal motor impairment was assessed by rotorod test and the estimation of various liver enzymes was performed to check the magnitude of liver toxicity posed by the synthesized compounds. Compounds 3d and 3k displayed comparable anticonvulsant activity... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314711 Fri, 14 Oct 2011 04:00:00 +0100 5314711 http://www.medworm.com/index.php?rid=5314720&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000256 AbstractA series of gatifloxacin, ciprofloxacin, and 8‐OCH3 ciprofloxacin coumarin derivatives with remarkable improvement in lipophilicity as compared to the parent fluoroquinolones was designed, synthesized, and characterized by 1H‐NMR, MS, and HRMS. These derivatives were evaluated for their in‐vitro activity against Mycobacterium smegmatis CMCC 93202 and MTB H37Rv ATCC 27294. All of the synthesized compounds were less active than the parent compounds against M. smegmatis CMCC 93202, but the activity of compound 6 was found to be 2–8‐fold more potent than ciprofloxacin, 8‐OCH3 ciprofloxacin, moxifloxacin, and rifampin, and comparable to gatifloxacin against MTB H37Rv ATCC 27294. These results indicated that the lipophilicity of the tested compounds is not the sole parameter ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314720 Wed, 12 Oct 2011 04:00:00 +0100 5314720 http://www.medworm.com/index.php?rid=5314719&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.200900164 AbstractA short and effective synthesis of ethyl 3‐(3‐aminophenyl)propanoate is presented, employing a tandem Knoevenagel condensation/alkylidene reduction of 3‐nitrobenzaldehyde with Meldrum's acid in TEAF (triethylammonium formate) followed by reduction of the intermediate 3‐(3‐nitrophenyl)propanoic acid by stannous chloride in ethanol. The use of stannous chloride as the reducing agent in ethanol enabled the simultaneous esterification of the carboxylic acid. Thus, stannous chloride was acting simultaneously as a Lewis acid, which activates the carboxylic acid towards a nucleophilic attack by ethanol.Ethyl 3‐(3‐aminophenyl)propanoate, an important precursor of biologically active compounds, was prepared in a two‐step procedure by means of Meldrum's acid in TEAF (triethyl... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314719 Wed, 12 Oct 2011 04:00:00 +0100 5314719 http://www.medworm.com/index.php?rid=5314718&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100078 AbstractNovel series of pyrazole derivatives were synthesized and tested for their in vivo anti‐malarial activity using mice infected with chloroquine sensitive P. berghei at a dose level of 50 µmol/kg. The most active compounds were further tested in vitro against chloroquine resistant (RKL9) strain of P. falciparum. The in vivo anti‐malarial activity study indicated that compounds 2a, 2b, 8a and 8b had mean percent suppression of 85%, 83%, 95% and 97%, respectively at equimolar dose level of the standard drug chloroquine diphosphate. Moreover, compounds 2a, 2b, 8a and 8b showed in vitro IC50 values lower (p < 0.05) than that of the standard drug chloroquine phosphate (0.188 ± 0.003  µM) using the RKL9 strain. Compound 8b was the most active with IC50 of 0.033 ±... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314718 Wed, 12 Oct 2011 04:00:00 +0100 5314718 http://www.medworm.com/index.php?rid=5314717&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100188 AbstractA series of novel 7‐alkoxyl substituted indolizinoquinoline‐5,12‐dione derivatives were synthesized. The cholinesterase inhibition assays indicated that most synthesized compounds exhibited good activity for acetylcholinesterase (AChE) and high selectivity index of AChE over butyrylcholinesterase (BuChE). Compound 12b exhibited the most potent AChE inhibitory activity with an IC50 value of 0.068 µM and the highest selectivity index of 144. Kinetic study of AChE indicated that a mixed type of inhibition pattern existed for these indolizinoquinoline‐5,12‐dione derivatives. Molecular docking study indicated that compound 12b could bind to both the catalytically active site and the peripheral anionic site of AChE.A series of novel 7‐alkoxyl substituted indolizinoquinolin... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314717 Wed, 12 Oct 2011 04:00:00 +0100 5314717 http://www.medworm.com/index.php?rid=5314716&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100171 Abstract4,6‐Dimethyl‐1H‐pyrazolo[3,4‐b]pyridine‐3‐amine (1) was used as a key intermediate for the synthesis of imidazolopyrazole derivatives 7–11 upon interaction with 3‐(2‐bromoacetyl)‐2H‐chromen‐2‐one (2), 2‐(benzothiazol‐2‐yl)‐4‐chloro‐3‐oxobutanenitrile (3), 2,3‐dibromonaphthalene‐1,4‐dione (4), naphtha[2,3‐b]oxirene‐2,7‐dione (5), 2,5‐dichloro‐3,6‐dihydroxyhexa‐2,5‐diene‐1,4‐dione (6), respectively. Acetylation of 11 afforded the bis‐acetyl 12. Also, the imidazolopyrimidine 15 was prepared via treatment of 1 with sodium 3,4‐dioxo‐3,4‐dihydronaphthalene‐1‐sulfonate (13) in DMF followed by cyclization of the bis‐pyrazolopyrimidine 14 with glacial acetic acid. On the other hand, compound 1 was reacted with (... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314716 Wed, 12 Oct 2011 04:00:00 +0100 5314716 http://www.medworm.com/index.php?rid=5314715&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100080 AbstractMethylenebisphosponic acid tetraethyl ester (1) was added to 2‐azido‐7a–e and 2‐chloroquinoline‐3‐chalcones 10a–e in boiling sodium ethanolate solution to give, via Michael addition, tetrazolo[1,5‐a]quinoline‐8a–d, 13a and 2‐chloroquinoline‐based bisphosphonates 11a–d, 14a in E‐configuration. Further acid hydrolysis afforded the respective BP‐acid analogues E‐9a–d, 12a–d, 13b, and 14b in excellent yields. Anti‐tumor activity screening for the new BP‐acids at a dose of 10 µM utilizing 44 different human tumor cell lines representing breast, ovary, prostate, lung, and CNS cancer as well as leukemia and melanoma was carried out. Eight of ten tested compounds exhibited remarkable anti‐tumor activity against breast and prostate cancer, and a ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314715 Wed, 12 Oct 2011 04:00:00 +0100 5314715 http://www.medworm.com/index.php?rid=5304600&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100133 AbstractIn the present study, a new series of ethyl 2‐(substituted benzylthio)‐4‐(3′‐(ethoxycarbonyl)‐biphenyl‐4‐yl)‐6‐methyl‐1,4‐dihydropyrimidine‐5‐carboxylate derivatives was synthesized. The newly synthesized compounds were characterized by 1H‐NMR, mass and C, H, N analyses. All newly synthesized compounds were screened for their antibacterial (Escherichia coli, Staphylococcus aureus, Pseudomonas aeruginosa, Streptococcus pyogenes and Klebsiella pneumoniae) and antifungal (Aspergillus flavus, Aspergillus fumigatus, Candida albicans, Penicillium marneffei and Trichophyton mentagrophytes) activity. The results revealed that all synthesized compounds have a significant biological activity against the tested microorganisms. Compounds 8a, 8b, 8c, 8e, 8f, 8i, an... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5304600 Tue, 11 Oct 2011 04:00:00 +0100 5304600 http://www.medworm.com/index.php?rid=5304599&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100144 AbstractRecently, we identified highly potent agonists of the human histamine H4 receptor (hH4R) among a series of imidazolylbutylcyanoguanidines. Aiming at improved selectivity for the hH4R relative to the H3 receptor (hH3R), the flexible tetramethylene linker connecting imidazole ring and cyanoguanidine group was replaced by conformationally restricted carbocycles. Introduction of a para‐ or a meta‐phenylene spacer yielded only very weakly active compounds at both hH3R and hH4R (investigated in [35S]GTPγS binding assays using Sf9 insect cell membranes expressing hHxR subtypes). By contrast, the incorporation of a more flexible cyclohexane‐1,4‐diyl linker resulted in EC50 or KB values ≥110 nM at hH4R and hH3R. Quality of action, potency and receptor subtype selectivity of the i... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5304599 Tue, 11 Oct 2011 04:00:00 +0100 5304599 http://www.medworm.com/index.php?rid=5304598&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000335 AbstractThe synthesis and in‐vitro biological evaluation of antifungal activities of a series of 1,2‐trans glycosphingolipids (GSL) against Candida albicans, Candida parapsilosis, and Candida tropicalis were described. The preliminary study indicated that the sort of sugar moiety of GSLs affected their antifungal activities and selectivities towards the three Candida species, and the permeability might not be the sole parameter affecting their antifungal properties as presumed before, which would bring new clues to understand the antifungal profile for these types of compounds.Antifungal activities of 1,2‐trans glycosphingolipids were tested against three Candida species. The results indicated that the sort of sugar moiety affected their antifungal activities and selectivities. In ad... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5304598 Tue, 11 Oct 2011 04:00:00 +0100 5304598 http://www.medworm.com/index.php?rid=5304597&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000312 AbstractA series of 6‐benzoyl‐, 6‐arylthio‐ and 6‐arylsulfonyl‐4‐amino‐2(1H)‐quinazolinones and ‐2,4(1H,3H)‐quinazolinediones were prepared. They were evaluated in vitro for their cytotoxicity against the NCI‐60 cancer cell lines.A series of 6‐benzoyl‐, 6‐arylthio‐ and 6‐arylsulfonyl‐4‐amino‐2(1H)‐quinazolinones and ‐2,4(1H,3H)‐quinazolinediones were prepared. They were evaluated in vitro for their cytotoxicity against the NCI‐60 cancer cell lines. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5304597 Tue, 11 Oct 2011 04:00:00 +0100 5304597 http://www.medworm.com/index.php?rid=5285894&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100072 AbstractIn an attempt to find a new and a safer drug for tuberculosis, we have synthesized a series of fluoronitrobenzothiazolopyrazolines for antitubercular activity. The series comprises three subclasses: fluorobenzothiazolopyrazolines (11a–f), fluoronitrobenzothiazolopyrazoline, nitro group at 5th position (12a–f) and 4th position (13a–f). All compounds were screened for their in‐vitro antitubercular activity against Mycobacterium tuberculosis H37Rv strain by using Middlebrook 7H‐9 broth. An introduction of NO2 group at 5th position of benzothiazole ring (12a–f) increased the antitubercular activity whereas introduction of NO2 group at 4th position (13a–f) was found to decrease the activity remarkably. Two compounds from each series showing good antitubercular activi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5285894 Wed, 05 Oct 2011 04:00:00 +0100 5285894 http://www.medworm.com/index.php?rid=5285893&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100112 AbstractThe reductive alkylation of amines procedure was applied for the synthesis of aripiprazole 1a, buspirone 1b, and NAN‐190 1c.The reductive alkylation of amines procedure has been applied for the synthesis of aripiprazole 1a, buspirone 1b, and NAN‐190 1c. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5285893 Wed, 05 Oct 2011 04:00:00 +0100 5285893 http://www.medworm.com/index.php?rid=5336074&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100251 AbstractIn an attempt to find a new class of antimicrobial agents, a series of benzothiazoles, 1,3‐thiazolo[5,4‐b]pyridines, 4H‐3,1‐benzothiazines, naphtho[2,3‐d][1,3]thiazole‐4,9‐diones and other related compounds containing a 2,4‐dihydroxyphenyl moiety were prepared. They were obtained via the reaction of aryl‐modified sulfinyl[bis(2,4‐dihydroxyphenylmethanethione)]s with appropriate commercial chemical reagents in the endocyclization processes. The MIC values of the compounds towards eight reference bacterial strains were assessed by the two‐fold serial micro‐dilution broth method. They exhibited inhibitory effects against the Gram‐positive strains tested opposite to Gram‐negative ones. Some compounds were more effective than the reference drug. 4‐(6‐Chlo... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5336074 Sat, 01 Oct 2011 04:00:00 +0100 5336074 http://www.medworm.com/index.php?rid=5314709&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100212 AbstractA new series of benzo[6,7]cyclohepta[1,2‐d]triazolo[4,3‐a]pyrimidines 8a–l was synthesized via reaction of heterocyclic thione 4 or its methyl derivatives 10 with hydrazonoyl halides 5a–l. Also, reaction of compound 4 with a mixture of chloroacetic acid and aromatic aldehyde derivatives gave benzo[6,7]cyclohepta[1,2‐d]thiazolo[3,2‐a]pyrimidin‐3‐ones 12–14. The microanalyses and spectral data of the synthesized compounds are in full agreement with their molecular structure. All the newly synthesized products were screened against 5α‐reductase and showed activities with good ED50 for all compounds. A new series of benzo[6,7]cyclohepta[1,2‐d] triazolo[4,3‐a]pyrimidines 8a–l was synthesized via reaction of heterocyclic thione 4 or its methyl derivatives 10 wi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5314709 Sat, 01 Oct 2011 04:00:00 +0100 5314709 http://www.medworm.com/index.php?rid=5304601&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190009 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5304601 Sat, 01 Oct 2011 04:00:00 +0100 5304601 http://www.medworm.com/index.php?rid=5304596&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000224 AbstractThe synthesis and anti‐Candida activity of 1‐[(3‐aroyloxy‐3‐phenyl)propyl]‐1H‐imidazoles 5a–f and 1‐[(3‐alkyl/aralkyl/phenyl‐3‐phenyl)propan‐3‐ol]‐1H‐imidazoles 5g–j are reported. The influence of the ester formation and different substitutions on the anti‐Candida activity of the alcohol 4 was investigated. Among the newly developed bioactive chemical entities, compounds 5b and 5c displayed minimum inhibitory concentrations (MICs) against Candida albicans and Candida pseudotropicales comparable to that of tioconazole and more potent than miconazole.The target compounds 1‐[(3‐aroyloxy‐3‐phenyl)propyl]‐1H‐imidazoles 5a–f were obtained in four steps starting from acetophenone 1 whereas 1‐[(3‐alkyl/aralkyl/phenyl‐3‐phenyl)propan... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5304596 Sat, 01 Oct 2011 04:00:00 +0100 5304596 http://www.medworm.com/index.php?rid=5274083&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100056 AbstractWe herein disclose a series of novel pyrrole derivatives 1–4 and pyrrolo[2,3‐d]pyrimidine derivatives 6–11 as novel potent anti‐inflammatory compounds. The structures were confirmed by IR, 1H‐NMR, and MS. Some newly synthesized compounds were examined for their in‐vivo anti‐inflammatory activity. Several derivatives showed a promising anti‐inflammatory activity compared to ibuprofen. In this paper, we examine and discuss the structure–activity relationships and anti‐inflammatory activities of these compounds.A series of heterocyclic compounds as potential anti‐inflammatory agents was synthesized and evaluated. Several derivatives as e.g. 6–11 showed a promising anti‐inflammatory activity compared to ibuprofen. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5274083 Thu, 29 Sep 2011 04:00:00 +0100 5274083 http://www.medworm.com/index.php?rid=5274082&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000402 AbstractHomocamptothecin (hCPT) is a camptothecin (CPT) homologue with the insertion of a methylene (CH2) spacer between the alcohol moiety and carbonyl group of the classical six‐membered α‐hydroxylactone ring. This modification provides higher lactone stability and did not impair its activity against topoisomerase I (Topo I), but rather appears to improve it compared to CPT. In an attempt to improve the antitumor activity of homocamptothecins, a series of novel hCPT derivatives conjugating with dihydropyrimidine (DHPM) derivatives was designed and synthesized based on a synthetic route which couples 7‐formylhomocamptothecin with different dihydropyrimidine derivates. Most of the synthesized compounds exhibited good antiproliferative activity on tumor cell lines A549, MDA‐M... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5274082 Thu, 29 Sep 2011 04:00:00 +0100 5274082 http://www.medworm.com/index.php?rid=5274081&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000267 AbstractA series of novel (thio)ureas containing the pyrimidinyl group was designed and synthesized. Their in‐vitro antitumor activity against different human tumor cells was examined. Some of the compounds showed potential antitumor activity, which provided some hints for further studies on structure modification.A series of novel (thio)urea derivatives was designed and synthesized. The in‐vitro preliminary bioassay data showed that compound 4k was found to have more potent cytotoxic activities against some human tumor cells than 5‐FU. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5274081 Thu, 29 Sep 2011 04:00:00 +0100 5274081 http://www.medworm.com/index.php?rid=5274080&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100093 AbstractA new descriptor, SVEEVA (principal component scores vector of electronic eigenvalue descriptors), was derived from principal component analysis (PCA) of a matrix of 220 electronic eigenvalue descriptors of coded amino acids. SVEEVA scales were then applied in three panels of peptide quantitative structure‐activity relationship (QSAR) that were modeled by partial least squares regression (PLS). The obtained models with the correlation coefficient (), cross‐validation correlation coefficient () were 0.894 and 0.839 for 58 angiotensin‐converting enzyme inhibitors, 0.995 and 0.949 for 12 antimicrobial polypeptides, and 0.995 and 0.976 for 20 thromboplastin inhibitors. Satisfactory results showed that information related to biological activity can be systemically expressed by SVE... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5274080 Thu, 29 Sep 2011 04:00:00 +0100 5274080 http://www.medworm.com/index.php?rid=5260986&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000223 AbstractA new series of gallic hydrazones containing an indole moiety was synthesized through the reaction of gallic hydrazide and different indole carboxaldehydes. Their antioxidant activities were determined on DPPH radical scavenging and inhibition of lipid peroxidation. The in‐vitro cytotoxic activities of the compounds were evaluated against HCT‐116 (human colon cancer cell line) and MCF‐7 (estrogen‐dependent human breast cancer cell line) by the MTT method. An attempt to correlate the biological results with their structural characteristics has been done. A limited positive structure activity relationship was found between cytotoxic and antioxidant activities.Gallic acid derivatives are naturally occurring compounds with interesting biological properties. Similarly, indolic c... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5260986 Tue, 27 Sep 2011 04:00:00 +0100 5260986 http://www.medworm.com/index.php?rid=5260985&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000280 AbstractSynthesis of 1‐substituted‐1,3,2‐diazaphosphole 1‐oxides (3a–l) were accomplished via a two‐step process. It involves the preparation of diazaphospholo 1‐oxide monochloride intermediate (2) and its subsequent reaction with phenols/amino acid esters in dry THF in the presence of triethylamine at 40–45°C. The structures of newly synthesized compounds were characterized by spectral and elemental analysis. The title compounds were evaluated for their in‐vitro antioxidant properties.A series of new 1,3,2‐diazaphosphole‐2‐oxides 3a–l have been synthesized and evaluated for their antioxidant properties. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5260985 Tue, 27 Sep 2011 04:00:00 +0100 5260985 http://www.medworm.com/index.php?rid=5260984&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000375 AbstractSynthesis of a new series of 3,4‐diarylpyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375P human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The biological results indicated that five synthesized compounds (Ig, Ii, IIc, IIg, and IIh) exhibited similar activity to Sorafenib. In addition, three compounds (IIa, IIb, and IIi) were more potent than Sorafenib. Among all of these derivatives, compound IIa which has dimethylamino and phenolic moieties showed the most potent antiproliferative activity against A375P human melanoma cell line. Virtual screening was carried out through docking of the most potent compound IIa into the domain of V600E‐b‐Raf and the binding mode ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5260984 Tue, 27 Sep 2011 04:00:00 +0100 5260984 http://www.medworm.com/index.php?rid=5250867&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000263 Abstract3‐Acetylcoumarin (1) was utilized as a key intermediate for the synthesis of 2‐aminothiazole derivative 3via bromination of 1 to afford acetylbromide 2 followed by treatment with thiourea or via Biginelli reaction of 1. Treatment of 3 with 5‐chloro‐3‐methyl‐1‐phenyl‐1H‐pyrazole‐4‐carbaldehyde, 2‐methyl‐4H‐benzo[d][1,3]oxazin‐4‐one, furo[3,4‐b]pyrazine‐5,7‐dione or 2‐methyl‐5,6,7,8‐tetrahydro‐4H‐benzothieno[2,3‐d][1,3]oxazin‐4‐one afforded diazine derivatives 4–7. Also, pyridopyrimidine 8 was obtained via a one pot reaction of 6‐aminothiouracil, p‐chlorobenzaldehyde and 3‐acetylcoumarin. Moreover, refluxing of 6‐aminothiouracil with one equivalent amount of 2 afforded the thiazolopyrimidine 9, while the pyrrolothiazolop... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5250867 Fri, 23 Sep 2011 04:00:00 +0100 5250867 http://www.medworm.com/index.php?rid=5250866&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100068 AbstractIn search of pharmacologically active potent compounds, a series of carbonyl‐amide linkage based new benzimidazole derivatives were synthesized from acid, aldehydes and isocyanide at ambient temperature via Passerini reaction. All the compounds synthesized were screened for their potential anti‐inflammatory, antidiabetic and anticonvulsant properties. The results revealed that compounds 2i and 2j were found to be the most potent anti‐inflammatory agents, while compounds 2a, 2c, 2e, 2f, 2i and 2j showed increased antidiabetic activity than the reference drugs and 2a, 2g, 2h, 2i and 2j were found to be the main structural requirement for maintaining anticonvulsant activity.One‐pot synthesis of carbonyl‐amide linkage based new benzimidazole derivatives as potent anti‐infla... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5250866 Fri, 23 Sep 2011 04:00:00 +0100 5250866 http://www.medworm.com/index.php?rid=5250865&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100103 AbstractIn an attempt to develop potent antitumor agents, a series of novel 2‐hydrazonylpyrido[2,3‐b]pyrazin‐3(4H)‐one derivatives were designed and synthesized. All the prepared compounds were screened for their cytotoxic activities against A549, MDA‐MB‐231 and HT‐29 cell lines in vitro. Pharmacological data indicated that five of the target compounds showed cytotoxicity against A549 cell line below a concentration of 1 µM. Compound 15g was the most potent one with IC50 values of 0.19, 2.11 and 2.15 µM against A549, MDA‐MB‐231 and HT29 cell lines, respectively.A series of 2‐hydrazonylpyrido[2,3‐b]pyrazin‐3(4H)‐one derivatives was designed and synthesized. Preliminary structure–activity relationships suggested that compounds with 4‐methoxyphenyl or 4‐(... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5250865 Fri, 23 Sep 2011 04:00:00 +0100 5250865 http://www.medworm.com/index.php?rid=5237999&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000346 AbstractA series of previously unreported α‐hydroxy hydrazonates were synthesized and tested for their antimalarial properties. Structure optimization of the antiplasmodially active α‐hydroxy hydrazonate III furnished derivatives with strong in‐vitro antimalarial activity against 3D7 strains of Plasmodium falciparum with IC50 values lower than 2.0 µM.Novel α‐hydroxy hydrazonates were prepared and evaluated as antiplasmodials. Remarkable antiplasmodial activity was ascertained for compounds 4r, 5d and 4q with IC50 values of 0.6, 0.85 and 1.1 µM, making these α‐hydroxy hydrazonates promising candidates for further drug design. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5237999 Tue, 20 Sep 2011 04:00:00 +0100 5237999 http://www.medworm.com/index.php?rid=5237998&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100001 AbstractIn research for promising antibacterial and antifungal compounds, a series of 2‐aryl 3‐[1,2,4]triazol‐5‐yl 4‐thiazolidinones 1 were synthesized by a domino reaction of 5‐amino‐1H‐[1,2,4]triazoles 3, aromatic aldehydes, and α‐mercaptoacids in boiling toluene in the presence of molecular sieves 4 Å. Of the twenty novel 3‐[1,2,4]triazol‐5‐yl 4‐thiazolidinone derivatives, four compounds 2‐benzo[d][1,3]dioxol‐6‐yl‐3‐[(3‐morpholin‐4‐yl)‐1H‐1,2,4‐triazol‐5‐yl)]‐1,3‐thiazolidin‐4‐one (1i), 2‐(4‐chlorophenyl)‐5‐methyl‐3‐[3‐(4‐methylpiperazin‐1‐yl)‐1H‐1,2,4‐triazol‐5‐yl]‐1,3‐thiazolidin‐4‐one (1p), 2‐benzo[d][1,3]dioxol‐6‐yl‐3‐[3‐(4‐methylpiperazin‐1‐yl)‐1H‐1,2,4‐triazo... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5237998 Tue, 20 Sep 2011 04:00:00 +0100 5237998 http://www.medworm.com/index.php?rid=5184218&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100125 AbstractA series of melatonin analogs obtained by the replacement of the ether methyl group with larger arylalkyl and aryloxyalkyl substituents was prepared in order to probe the melatonin receptors for MT1‐selectivity. The most MT1‐selective agents 11 and 15 were substituted with a Ph(CH2)3 or a PhO(CH2)3 group. Compounds 11 and 15 displayed 11.5‐fold and 11‐fold higher affinity for the MT1 receptors than for the MT2 subtype. Interestingly, in our binding assay 11 and 15 have shown considerably higher MT1‐affinity and selectivity than the reference ligand, the dimeric agomelatine 1a.The synthesis and pharmacological evaluation of a novel series of MLT analogs obtained by replacing the ether methyl group with arylalkyl and aryloxyalkyl moieties is described here. The results indi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5184218 Thu, 01 Sep 2011 23:00:00 +0100 5184218 http://www.medworm.com/index.php?rid=5184217&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100095 AbstractSeven benzylamino derivatives of podophyllotoxin 8a–8g were synthesized and their chemical structures were confirmed by IR, 1H‐NMR, 13C‐NMR and ESI‐MS spectral analyses. Their abilities to inhibit the growth of cancer cells A549, HCT‐116 and HepG2, were investigated by MTT assay. Compound 8b possessed the highest cytotoxicity on cancer cell lines with average IC50 values of 3.8 µM. All we synthetic compounds were cytotoxic against three cancer cell lines at the micromolar range, indicating podophyllotoxin derivatives with structural modification of benzylamino possess potent antitumor activity.Seven benzylamino derivatives of podophyllotoxin (8a–8g) were synthesized and screened for cytoxic activity. All seven compounds possess promising antitumor activity, especiall... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5184217 Thu, 01 Sep 2011 23:00:00 +0100 5184217 http://www.medworm.com/index.php?rid=5285892&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100092 AbstractFive new immunomodulators 1a–1e by using a trans‐4‐alkyl‐substituted cyclohexane to replace the flexible C8 alkyl chain of Fingolimod were synthesized. For in‐vitro test, the compounds were dissolved in DMSO as a stock solution and diluted to a desired concentration with RPMI 1640 nutrient solution. For in‐vivo test, the compounds were prepared in pathogen‐free saline containing 0.5% DMSO. These new immunomodulators displayed more potent immunoinhibitory activities in vitro and moderate immunomodulating activities in vivo. They show therapeutic effects on DNFB‐induced DTH reaction and inhibitory effects on the antigen‐specific T‐cell proliferation.Five new immunomodulators 1a–1e by using a trans‐4‐alkyl‐substituted cyclohexane to replace the flexible C8 ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5285892 Thu, 01 Sep 2011 04:00:00 +0100 5285892 http://www.medworm.com/index.php?rid=5274079&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100122 This study shows how and to what extent the position of side chain substituents affects telomerase activity. Four series of compounds containing an anthraquinone‐linked moiety and symmetrical or asymmetrical aminoacyl residues have been synthesized and evaluated for their inhibitory effects towards telomerase and hTERT expression. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5274079 Thu, 01 Sep 2011 04:00:00 +0100 5274079 http://www.medworm.com/index.php?rid=5260983&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100094 AbstractA series of 4α/4β‐imidazolyl podophyllotoxin analogues have been designed and synthesized. All of the compounds were evaluated for their anticancer activity against a panel of three human cancer cell lines. Within the cell lines tested, some of the synthesized compounds showed promising anticancer activity. Compound 12, in particular, exhibited remarkable cytotoxicity, demonstrating effects against all tumor cell lines, including the K562/ADM cell line.A series of podophyllotoxin analogues have been synthesized and evaluated for their cytotoxic activity on human cancer cell lines. Compound 12 exhibited remarkable cytotoxicity, demonstrating effects against all tumor cell lines, including the K562/ADM cell line. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5260983 Thu, 01 Sep 2011 04:00:00 +0100 5260983 http://www.medworm.com/index.php?rid=5250864&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100108 AbstractA series of novel N1‐substituted‐N2,N2‐diphenyl oxalamides 3a–l were synthesized in good yield by stirring diphenylcarbamoyl formyl chloride (2) and various substituted aliphatic, alicyclic, aromatic, heterocyclic amines in DMF and K2CO3. Also 2‐substituted amino‐N,N‐diphenylacetamides 5a–m were designed by pharmacophore generation and synthesized by stirring 2‐chloro‐N,N‐diphenylacetamide (4) and various substituted amines in acetone using triethyl amine as a catalyst. All the synthesized compounds were screened for anticonvulsant activity in Swiss albino mice by MES and ScPTZ induced seizure tests. Neurotoxicity screening and behavioral testing was also carried out. Some of the synthesized test compounds were found to be more potent than the standard drug.A ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5250864 Thu, 01 Sep 2011 04:00:00 +0100 5250864 http://www.medworm.com/index.php?rid=5237997&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100082 AbstractA novel series of indolin‐2‐one derivatives containing the 4‐thiazolidinone moiety (5a–5p) was synthesized and the cytotoxicity of these derivatives was evaluated in vitro against three human cancer cell lines (HT‐29, H460 and MDA‐MB‐231) by standard MTT assay. Some prepared compounds exhibited significant cytotoxicity against different human cancer cell lines. Several potent compounds were further evaluated against one normal cell line (WI‐38). In particular, the promising compound 5h showed remarkable cytotoxicity and selectivity against HT‐29 and H460 cancer cell lines (IC50 = 0.016 µmol/L, 0.0037 µmol/L, respectively).A novel series of indolin‐2‐one derivatives containing the 4‐thiazolidinone moiety (5a‐5p) was synthesized and evaluated in vi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5237997 Thu, 01 Sep 2011 04:00:00 +0100 5237997 http://www.medworm.com/index.php?rid=5184219&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190008 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5184219 Wed, 31 Aug 2011 23:00:00 +0100 5184219 http://www.medworm.com/index.php?rid=5184216&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100005 Abstract36 Novel heterocyclic chalcone derivatives were synthesized and tested for their anti‐bacterial activity. Some compounds presented good anti‐microbial activities against Gram‐positive bacteria (including the multidrug‐resistant clinical isolates). This class of compounds presented high potency against Streptococcus mutans, among which the derivatives F2 with an MIC of 2 µg/mL was as active as the standard drug (norfloxacin) and less active than oxacillin. All the compounds did not inhibit the growth of Gram‐negative bacteria (Escherichia coli CCARM 1924 or Escherichia coli CCARM 1356) at 64 µg/mL.36 novel heterocyclic chalcone derivatives were synthesized and tested for their anti‐bacterial activity. All tested compounds did not inhibit the growth of Gram‐negati... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5184216 Wed, 31 Aug 2011 23:00:00 +0100 5184216 http://www.medworm.com/index.php?rid=5170499&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000238 AbstractA series of novel compounds 7–43 were prepared via the condensation of enaminones 4a–h and the guanidines carbonate 6a–f. The structures of these newly synthesized compounds were confirmed by 1H‐NMR, MS, EA and IR. All the compounds were tested for their cytotoxic activity in vitro against human cancer cell lines including Ishikawa, A549, BEL‐7404, SPC‐A‐01 and SGC‐7901. Most of them showed moderate cytotoxic against the tested cell lines. Among them, the most potent compounds 9 and 30 exhibited more efficient activity against Ishikawa, A549.Thiazolyl‐pyrimidines were synthesized by the general pyrimidine condensation of Bredereck and their in‐vitro anticancer activities were evaluated. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5170499 Sun, 28 Aug 2011 23:00:00 +0100 5170499 http://www.medworm.com/index.php?rid=5170498&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000367 AbstractA structurally diverse series of Δ4,5‐uronamide derivatives have been chemically synthesized starting from D‐glucuronic acid itself by means of acetylation, activation, amide bond formation and base‐catalyzed elimination protocols. Structure elucidation for all products along with optimization of the synthetic steps is described. The synthesized compounds were evaluated for their in‐vitro anti‐tumor activity against MCF‐7, TK‐10 and UACC‐62 cell lines. The compounds 5, 11, 13, 15 and 16 were the most active against TK‐10 cell line. On the other hand, the most active compounds against the MCF‐7 cell line were 11 and 15. However, compounds 5, 7, 11, 13, 15 and 16 were the most active against the UACC‐62 cell line.A highly efficient and practical method was desc... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5170498 Sun, 28 Aug 2011 23:00:00 +0100 5170498 http://www.medworm.com/index.php?rid=5162013&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000309 AbstractWe herein describe the synthesis of 15 novel 13‐membered cyclic enediyne derivatives using simple and straightforward approach. Representative examples were screened for their anticancer activities on 60 different human tumor cell lines representing various histologies viz. leukemia, melanoma, and cancers of lung, colon, kidney, ovary, breast, prostate, and central nervous system. The enediyne derivatives with halogen substitutions, especially fluorides were found to be active against most of the cell lines. The initial results indicates marginal to good inhibition for the growth of tumor cells for several cell lines, which shows the potential of these class of compound towards anticancer application.15 novel 13‐membered cyclic enediyne derivatives using a simple and straightfo... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5162013 Wed, 24 Aug 2011 23:00:00 +0100 5162013 http://www.medworm.com/index.php?rid=5162012&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000357 In this study a novel series of 1,2,4‐triazole, imidazole, benzoimidazole, and benzotriazole derivatives was designed as inhibitors of cytochrome P450 14α‐demethylase (14DM). These structures were docked into the active site of MT‐CYP51, using Autodock program. Sixteen compounds with the best binding energy were synthesized. The chemical structures of the new compounds were confirmed by elemental and spectral (1H‐NMR and Mass) analyses. All compounds were investigated for antifungal activity against Candida albicans, Candida tropicalis, Candida glabrata, Candida parapeilosis, Candida kruzei, Candida dubliniensis, Aspergillus fomigatus, Aspergillus flavus, Microsporum canis, Microsporum gypseum, Trichophyton mentagrophyte, Epidermophyton floccosum. Some compounds showed excellent i... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5162012 Wed, 24 Aug 2011 23:00:00 +0100 5162012 http://www.medworm.com/index.php?rid=5162011&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000363 AbstractThree series of novel artemisinin–guanidine hybrids 4a–4f, 8a–8h and 9a–9h have been facilely synthesized via four‐component reaction (aza‐Wittig reaction) and evaluated for their anti‐tumor activities against A549, HT‐29 and MDA‐MB‐231 cell lines in vitro. All of the tested compounds showed enhanced anti‐tumor activities with IC50 values ranging from 0.02 µM to 12.0 µM as compared to DHA (dihydroartemisinin). Among them, artemisinin derived dimers, compounds 9b (IC50 = 0.05 µM), 9d (IC50 = 0.06 µM) and 9f (IC50 = 0.02 µM) were found to be most active against HT29 cells.An efficient method to generate three series of novel artemisinin derivates using multi‐component reaction was developed. From the preliminary results we can conc... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5162011 Wed, 24 Aug 2011 23:00:00 +0100 5162011 http://www.medworm.com/index.php?rid=5162010&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000366 AbstractDeveloping new therapeutic agents that can overcome gastrointestinal injury and at the same time could lead to an enhanced anti‐inflammatory effect becomes an urgent need for inflammation patients. Thiazolyl and pyrrolyl steroids were synthesized via straight forward and efficient methods and their structures were established based on their correct elemental analysis and compatible IR, 1H‐NMR, 13C‐NMR, and mass spectral data. The dihydrothiazolyl‐hydrazonoprogesterone 12 and the aminopyrrolylprogesterone 16a showed anti‐inflammatory, antinociceptive, and anti‐ulcerogenic activity with various intensities. Edema were significantly reduced by both doses of tested compounds (25 and 50 mg/kg) at 2, 3, and 4 h post‐carrageenan. The high dose of compound 16a was the mos... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5162010 Wed, 24 Aug 2011 23:00:00 +0100 5162010 http://www.medworm.com/index.php?rid=5162009&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000391 AbstractIn an attempt to develop potent and selective anti‐tumor agents, three new series of artemisinin–chalcone hybrids 10a–10g, 11a–11g and 12a–12h were designed, synthesized and screened for their anti‐tumor activity against five cell lines (HT‐29, A549, MDA‐MB‐231, HeLa and H460) in vitro. Among compounds 10a–g and 11a–11g, most of them displayed enhanced activity and good selectivity toward HT‐29 and HeLa cell lines with IC50 values ranging from 0.12 to 0.85 µM as compared with DHA (dihydroartemisinin). Compounds 10a and 11a are most active toward HeLa cells with IC50 values of 0.12 and 0.19 µM. The results revealed that the presence of chalcone moiety is beneficial to their activity and selectivity. In addition, compounds 12a‐12h containing a ‘rever... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5162009 Wed, 24 Aug 2011 23:00:00 +0100 5162009 http://www.medworm.com/index.php?rid=5170497&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000382 In this study we tried to achieve comparable effects with [alkyne]silver or copper trifluoromethanesulfonate complexes which are more hydrophilic then the uncharged metalcarbonyl derivatives. All compounds were evaluated for growth inhibition against breast (MCF‐7, MDA‐MB 231) and colon cancer (HT‐29) cell lines and for COX‐1 and COX‐2 inhibitory effects at isolated isoenzymes. Pure ligands showed neither cytotoxic nor COX‐inhibitory effects. While the silver complexes of (but‐2‐ynyl)‐2‐acetoxybenzoate (But‐ASS‐Ag) and (but‐2‐yne‐1,4‐diyl)‐bis(2‐acetoxybenzoate) (Di‐ASS‐But‐Ag) were strong cytostatics, only the copper complex Di‐ASS‐But‐Cu was active. At the COX enzymes the complexes were more effective than their ligands and aspirin.Silver a... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5170497 Sun, 31 Jul 2011 23:00:00 +0100 5170497 http://www.medworm.com/index.php?rid=5162008&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000271 AbstractCoumarin and benzothiazole scaffolds can be found in a number of natural or synthetic antioxidants. In an effort to develop a novel radical scavenger and potential antioxidant, a series of coumarin derivatives containing 2‐methylbenzothiazoline motif and related compounds was synthesized and evaluated for their DPPH (1,1‐diphenyl‐2‐picrylhydrazyl) and ABTS•+ (2,2′‐azinobis(3‐ethylbenzothiazoline‐6‐sulfonic acid) radicals scavenging activities. Among them, 7‐hydroxy‐3‐(2‐methyl‐2,3‐dihydrobenzo[d]thiazol‐2‐yl)‐2H‐chromen‐2‐one (3e) has shown a significant free radical scavenging activity. From the structure–activity point of view, it was found that phenolic coumarin ring and benzothiazoline moiety in target compounds may contribute to th... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5162008 Sun, 31 Jul 2011 23:00:00 +0100 5162008 http://www.medworm.com/index.php?rid=5109646&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190007 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5109646 Sun, 31 Jul 2011 23:00:00 +0100 5109646 http://www.medworm.com/index.php?rid=5030624&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100077 AbstractThe synthesis of a series of certain polymethoxy chalcones and some derived pyrazole, pyrimidine, and thiazolopyrimidine ring structures is reported. Eleven compounds 4, 6, 9, 11, 14–17, 22, 24, and 25 were selected by the National Cancer Institute (NCI) to be screened for their in‐vitro anticancer activity, whereas all the synthesized compounds were evaluated for their in‐vitro antimicrobial activity. Compounds 4, 6, and 11 were found to possess a significant broad spectrum antitumor potential against most of the tested subpanel tumor cell lines. The pyrazolines 4 and 6 displayed remarkable growth inhibitory activities (GI50 MG‐MID values of 2.10 and 1.38 µM, respectively), together with moderate cytostatic effects (TGI MG‐MID values of 47.9 and 42.7 µM, respective... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5030624 Thu, 30 Jun 2011 23:00:00 +0100 5030624 http://www.medworm.com/index.php?rid=5010037&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190006 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=5010037 Thu, 30 Jun 2011 23:00:00 +0100 5010037 http://www.medworm.com/index.php?rid=4954621&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100101 AbstractA series of Cu(II), Co(II), Pt(II) and Zn(II) coordination compounds has been prepared by the reaction of the metal chlorides with pyrazine‐2‐carboxylic acid, pyridine‐2‐carboxylic acid, imidazole‐4‐carboxylic acid, benzimidazole‐2‐carboxylic acid and 1‐methylimidazole‐2‐carboxylic acid. The complexes were characterized by IR, UV‐VIS, elemental analysis, and some by 1H‐NMR, X‐ray crystallography, HPLC and LC/MS spectroscopy. All complexes consist of a 2:1 ratio of ligand to metal ion. IR and X‐ray crystallography show that coordination is through the nitrogen and carboxylate oxygen donor atoms of the ligand to form chelating rings. DFT calculations predict that the trans‐coordinated isomers are thermodynamically more stable than their cis‐forms. On... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4954621 Mon, 20 Jun 2011 23:00:00 +0100 4954621 http://www.medworm.com/index.php?rid=4954620&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100053 AbstractSeveral novel series of triazolophthalazine derivatives namely; pyrazolylethenyltriazolophthalazinones (4a–d), styryltriazolophthalazinones (5a,b), aryloxopropenyltriazolophthalazinones (7a,b), pyrazolinyl‐ (8a,b), (9a,b) and (10a–f), pyrazolyl‐ (11a–d), (1,2‐oxazol‐5‐yl)‐1,2,4‐triazolo[3,4‐a]phthalazin‐6(5H)‐ones (14a,b), triazolo[3,4‐a]phthalazin‐3‐yl‐pyridine‐3‐carbonitriles (12a,b), triazolo[3,4‐a]phthalazin‐3‐yl)ethylthioacetic acids (13a,b) and 2‐aryl‐5‐arylamino‐1H,5H‐pyrazolo[2″,3″‐1′,5′]imidazo[3′,4′‐1,5]‐1,2,4‐triazolo[3,4‐a]phthalazin‐12(13H)‐ones (15a–c) have been synthesized. The anti‐inflammatory activity of representative compounds has been studied. Compounds 8b, 10c, 10f, 11b, 12a, 1... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4954620 Mon, 20 Jun 2011 23:00:00 +0100 4954620 http://www.medworm.com/index.php?rid=4937256&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000397 AbstractFive licofelone ([2,2‐dimethyl‐6‐(4‐chlorophenyl)‐7‐phenyl‐2,3‐dihydro‐1H‐pyrrolizin‐5‐yl]acetic acid) nitric oxide donor conjugates were developed by a parallel synthesis approach. The biological screening revealed that compounds with a propyl (6b), butyl (6c), or octyl (6d) chain between licofelone and the nitric oxide donor exhibited high antiproliferative potency at MCF‐7 and MDA‐MB–231 breast cancer as well as at HT‐29 colon cancer cells. Moreover, 6b–d possessed at least 2‐fold higher cytotoxicity at MDA‐MB‐231 cells than the parent compound licofelone although they showed less inhibitory activity at COX‐1 and COX‐2. A correlation between COX inhibition and growth inhibitory properties is not visible. However, the high levels of n... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4937256 Wed, 15 Jun 2011 23:00:00 +0100 4937256 http://www.medworm.com/index.php?rid=4937255&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100020 AbstractIn an effort to establish new candidates with improved analgesic and anti‐inflammatory activities, we reported here the synthesis and in‐vivo analgesic and anti‐inflammatory evaluation of various series of 2‐substituted‐3a,4,9,9a‐tetrahydro‐4,9‐benzeno‐benz[f]isoindole‐1,3‐diones: [4‐Bromobutoxy] 6, 5‐bromopentoxy 7, [4‐(4‐phenylpiperazin‐1‐yl)butoxy] 9, [5‐(4‐phenylpiperazin‐1‐yl)pentoxy] 10, 2‐(2(4)‐(4‐phenylpiperazin‐1‐yl)‐2‐oxoethyl/4‐oxobutyl 17, 19, [2(4)‐(4‐methylpiperazin‐1‐yl]‐2‐oxoethyl/4‐oxobutyl 20, 22, [2(4)‐morpholino‐2‐oxoethyl/4‐oxobutyl] 23, 25, and 2(4)‐(piperidin‐1‐yl)2‐oxoethyl/4‐oxobutyl) 26 and 28. The newly synthesized compounds were characterized by (IR, 1H‐, 13C‐NM... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4937255 Wed, 15 Jun 2011 23:00:00 +0100 4937255 http://www.medworm.com/index.php?rid=4937254&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100055 AbstractThe synthesis and antitumor activity screening of novel isatin based conjugates with thiazolidine and pyrazoline moieties were performed. Reaction of 3,5‐diaryl‐4,5‐dihydropyrazoles with chloroacetyl chloride yielded starting 2‐chloro‐1‐(3,5‐diaryl‐4,5‐dihydropyrazol‐1‐yl)‐ethanones which were utilized in alkylation of isatin and 5‐bromoisatin. Thus, corresponding 1‐[2‐(3,5‐diaryl‐4,5‐dihydropyrazol‐1‐yl)‐2‐oxoethyl]‐1H‐indole‐2,3‐diones (1a–1d) have been obtained. The compounds 1a–1d have been used in Knoevenagel condensation with 4‐thiazolidinones for obtaining a series of 5‐ylidenederivatives 2a–2f and 3a–3d. The synthesized compounds were tested for their anticancer activity in NCI60 cell lines. Among the tested co... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4937254 Wed, 15 Jun 2011 23:00:00 +0100 4937254 http://www.medworm.com/index.php?rid=4937257&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100030 AbstractGlycyrrhetinic acid (GA) is a major ingredient of the dried extract of licorice roots; its antitumor activity is low compared to other members of the triterpenoic family. For example, oleanolic acid, betulin or betulinic acid are more cytotoxic with a pronounced activity for tumor cells. GA, however, is easily to earn, cheap and shows apoptotic effects on tumor cells – like the other triterpenoic acids. These facts bring GA and derivatives in the focus of our scientific interest. Here we tried to improve the poor cytotoxicity of GA by simple derivatization. Thus, we selected various glutamyl and aspartyl substituents for the synthesis of C(3) esters of GA methyl ester. A short (3‐5 steps) synthesis was elaborated that allowed to access more effective compounds. One compound, me... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4937257 Mon, 13 Jun 2011 23:00:00 +0100 4937257 http://www.medworm.com/index.php?rid=4977852&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000296 AbstractWe recently reported a series of 1‐acyl‐N‐(biphenyl‐4‐ylmethyl)pyrrolidine‐2‐carboxamides as AT1 receptor ligands. The most potent compound of the series, 1‐pentanoyl‐N‐{[2'‐(1H‐tetrazol‐5‐yl)biphenyl‐4‐yl]methyl}‐pyrrolidine‐2‐carboxamide, showed an interesting affinity for the receptor. To investigate the influence of structure variations on affinity, the synthesis of additional compounds belonging to this series has been performed. Biological tests run on the newly synthesized compounds on CHO‐hAT1 cells stably expressing the human AT1 receptor confirm our previous hypothesis, i.e. that, within this series, the length of the acyl chain, the substitution of the amidic group and the nature of the acidic one are crucial for the receptor inter... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4977852 Tue, 31 May 2011 23:00:00 +0100 4977852 http://www.medworm.com/index.php?rid=4954619&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000350 AbstractIn the last 20 years, a great variety of synthetic, low molecular weight MMP inhibitors (MMPIs) have been synthesized and tested, although none has reached clinical utility. Exploration of novel ZBGs and development of non‐hydroxamate MMPI has become a focus in current research. It's well‐known that polyphenols can produce beneficial effects on human health by their antioxidant properties as well as they have the ability to block gelatinase activity. In this work we tested a series of selected phenols as MMP inhibitors. The most interesting hit (B6) shows sub‐micromolar activity against MMP‐2 (IC50 0.59 ± 0.05 µM, LE = 1.07) and a fairly good selectivity spectrum.A screening of selected phenols against four matrix metalloproteinases is reported. Eight phenols sh... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4954619 Tue, 31 May 2011 23:00:00 +0100 4954619 http://www.medworm.com/index.php?rid=4937253&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201100109 AbstractThe synthesis of a series of novel N‐α‐galloylated isoglutamic acid γ‐amide peptidomimetics is described. Their enzymatic inhibition against aminopeptidase N (APN/CD13) and matrix metalloproteinase‐2 (MMP‐2) was tested. The preliminary activity assay revealed that most of the compounds displayed selective inhibition against APN as compared with MMP‐2, with IC50 values in a micromolar range. Within this series, compound 4 (IC50 = 10.2 ± 0.9 µM) demonstrated comparable APN inhibition as compared with the positive control bestatin (IC50 = 13.1 ± 0.7 µM), which might be a promising lead for further molecular optimizations.A new series of bi‐peptide analogues containing amino acid or organic acid residues as elongated hydrophobic substituents inse... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4937253 Tue, 31 May 2011 23:00:00 +0100 4937253 http://www.medworm.com/index.php?rid=4913847&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000160 AbstractA series of novel 7‐(3‐aminopyrrolo[3,4‐c]pyrazol‐5(2H,4H,6H)‐yl)‐6‐fluoro‐4‐oxo‐1,4‐dihydroquinoline‐3‐carboxylic acid derivatives was designed, synthesized and characterized by 1H‐NMR, MS and HRMS. These fluoroquinolones were evaluated for their in‐vitro antibacterial activity against representative Gram‐positive and Gram‐negative strains. Generally, all of the target compounds display rather weak potency against the tested Gram‐negative strains, but most of them exhibit good potency in inhibiting the growth of S. aureus including methicillin‐resistant Staphylococcus aureus (MRSA) and Staphylococcus epidermidis including methicillin‐resistant S. epidermidis (MRSE) (MIC: 0.125–8 µg/mL). In particular, the compound 9g is 2 to 32 fold mor... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4913847 Tue, 31 May 2011 23:00:00 +0100 4913847 http://www.medworm.com/index.php?rid=4895453&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190005 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4895453 Tue, 31 May 2011 23:00:00 +0100 4895453 http://www.medworm.com/index.php?rid=4864420&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000352 AbstractA number of secondary and tertiary amines bearing 2‐chloro‐6‐methylquinoline were synthesized by nucleophilic substitution reaction of 3‐(chloromethyl)‐2‐chloro‐6‐methylquinoline with substituted aromatic primary and secondary amines in presence of catalytic amount of triethylamine (TEA) and K2CO3. All the compounds were characterized by combined use of IR, 1H‐NMR, 13C‐NMR, mass spectral data, and microanalyses. The newly synthesized quinolinyl amines were screened in vitro for their antifungal activity against Aspergillus niger MTCC 281, Aspergillus flavus MTCC 277, Monascus purpureus MTCC 369, Penicillium citrinum NCIM 768 and for antibacterial activity strains viz. Escherichia coli NCTC 10418, Staphylococcus aureus NCTC 65710, and Pseudomonas aeruginosa NCTC ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4864420 Tue, 24 May 2011 23:00:00 +0100 4864420 http://www.medworm.com/index.php?rid=4864419&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000341 AbstractThe reaction of nucleophilic phosphacumulene and phosphallene ylides with different chromenone derivatives was investigated. Heterocycles and carbocycles of various ring sizes and heteroatom patterns such as pyrano‐, oxaphosphino‐, cyclopenta‐, phosphoranylidene cyclobutane‐, and phospholo‐chromenones were obtained. The antitumor (breast and liver) properties of some new compounds were performed in vitro. Some of these compounds were more potent than the comparative standard.Reactions of active phosphonium ylides with coumarin derivatives led to new heterocycles of various ring sizes and heteroatom patterns. Many of the new compounds revealed pronounced in‐vitro antitumor activities when tested against human MCF‐7 and HEPG2 carcinoma cell lines. The most promising res... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4864419 Tue, 24 May 2011 23:00:00 +0100 4864419 http://www.medworm.com/index.php?rid=4842995&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000281 AbstractIn an attempt to develop potent and selective anti‐tumor drugs, a series of novel 2‐amino‐thiazole‐5‐carboxylic acid phenylamide derivatives were designed based on the structure of dasatinib. All compounds were synthesized by a systematic combinatorial chemical approach. Biological evaluation revealed that N‐(2‐chloro‐6‐methylphenyl)‐2‐(2‐(4‐methylpiperazin‐1‐yl)acetamido)thiazole‐5‐carboxamide (6d) exhibited high antiproliferative potency on human K563 leukemia cells comparable to dasatinib. Against mammary and colon carcinoma cells 6d was either inactive (MDA‐MB 231) or distinctly less active (MCF‐7 and HT‐29: IC50 = 20.2 and 21.6 µM, respectively). Dasatinib showed at each cell line IC50 < 1 µM. The results of this structu... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4842995 Thu, 19 May 2011 23:00:00 +0100 4842995 http://www.medworm.com/index.php?rid=4842994&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000144 AbstractThe cancer chemotherapeutic potential of surfactant–cobalt(III) complexes, cis‐[Co(bpy)2(C14H29NH2)Cl](ClO4)2 · 3 H2O (1) and cis‐[Co(phen)2(C14H29NH2)Cl](ClO4)2 · 3 H2O (2) (bpy = 2,2′‐bipyridine, phen = 1,10‐phenanthroline) on MCF‐7 breast cancer cell was determined adopting MTT assay and specific staining techniques. The complexes affected the viability of the cells significantly and the cells succumbed to apoptosis as seen in the changes in the nuclear morphology and cytoplasmic features. Since the complex 2 appeared to be more potent, further assays were carried out on the complex 2. Single‐cell electrophoresis indicated DNA damage. The translocation of phosphatidyl serine and loss of mitochondrial potential was revealed by annexin V‐Cy3 sta... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4842994 Thu, 19 May 2011 23:00:00 +0100 4842994 http://www.medworm.com/index.php?rid=4842993&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000365 AbstractBased on the pharmacophore model of Glennon the conformationally restricted σ1 receptor ligand 2 with a 1,3‐dioxane moiety has been designed and synthesized. The three step synthesis (transacetalization with pentane‐1,3,5‐triol, tosylation, and nucleophilic substitution with benzylamine) provided diastereoselectively the cis‐configured 1,3‐dioxane 2 in good yields. The 1,3‐dioxane 2 represents a potent σ1 receptor ligand (Ki = 19 nM) with moderate selectivity over the σ2 subtype (Ki = 92 nM) and excellent selectivity against more than 60 other targets. Additionally the hERG K+ channel is not affected by 2. In the capsaicin assay 2 showed extraordinarily high analgesic activity with more than 70% analgesia at the very low dose of 0.25 mg/kg body weight, whic... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4842993 Thu, 19 May 2011 23:00:00 +0100 4842993 http://www.medworm.com/index.php?rid=4864418&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000183 AbstractA new series of 16 6‐chloro‐1,1‐dioxo‐7‐{4‐[(4‐R1‐phenyl)imino]‐4H‐3,1‐benzoxazin‐2‐yl}‐3‐(substituted amino)‐1,4,2‐benzodithiazines 7–22 was prepared in order to evaluate the cytotoxic activity against six human cancer cell lines. The structures of the new compounds were confirmed by IR, 1H‐, and 13C‐NMR, elemental analysis and in the cases of 11 and 31 by X‐ray crystal structure analysis. This analysis showed that contrary to our earlier report the structures contain a benzoxazine ring instead of the proposed quinazolinone ring. The bioassay indicated that the benzodithiazine derivatives 7–22 possess cancer cell growth‐inhibitory properties. Some compounds showed a high level of selectivity for certain cell lines. The most active comp... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4864418 Sat, 30 Apr 2011 23:00:00 +0100 4864418 http://www.medworm.com/index.php?rid=4842992&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000394 This study proves that the class of thienopyrimidines can potentially serve as lead structure for further optimization. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4842992 Sat, 30 Apr 2011 23:00:00 +0100 4842992 http://www.medworm.com/index.php?rid=4736264&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190004 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4736264 Fri, 22 Apr 2011 16:27:04 +0100 4736264 http://www.medworm.com/index.php?rid=4715722&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000141 AbstractSome new 2‐(2‐(4(4‐substitutedbenzoyl‐2‐methylphenoxy)acetyl)‐N‐(2‐substitutedphenyl) hydrazinecarbothioamides (4a–4j) and (4‐((5‐(2‐substitutedphenylamino)‐1,3,4‐oxadiazol‐2‐yl)methoxy)‐3‐substitutedphenyl)(phenyl)methanones (5a–5j) have been synthesized from 2‐(4‐(3‐substitutedbenzoyl)‐2‐methylphenoxy)acetohydrazides (3a, 3b). These newly synthesized compounds (4a–4j and 5a–5j) were characterized by elemental and spectral (IR, 1H‐NMR and MS) analysis. All the synthesized compounds have been screened for their antibacterial activity against both types of Gram negative and Gram positive bacteria. The most potent antibacterial compound of this series was compound 5i which has the low MIC 3.75–0.9375 µg/mL value. Both minimal... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4715722 Thu, 31 Mar 2011 23:00:00 +0100 4715722 http://www.medworm.com/index.php?rid=4677703&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190003 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4677703 Thu, 31 Mar 2011 23:00:00 +0100 4677703 http://www.medworm.com/index.php?rid=4665186&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000187 AbstractCoupling of 6‐benzyl‐5‐hydroxymethyluracil (1) with formaldehyde acetals followed by fluorination using (diethylamino)sulfur trifluoride (DAST) afforded 1‐alkenyloxymethyl and 1‐propargyloxymethyl 5‐fluoromethyl‐6‐benzyluracils 3a–c. 6‐(3,5‐Dimethylbenzyl)‐5‐ethyl‐1‐[(2‐fluoroethoxy)methyl]pyrimidine‐2,4(1H,3H)‐dione (6) was synthesized by fluorination of the corresponding hydroxy derivative 5. Sonogoshira reaction was performed on 6‐(3,5‐dimethylbenzyl)‐5‐ethyl‐1‐(4‐iodobenzyl)uracil (7) with propargyl alcohol to afford 8 which was fluorinated to give the fluoro propargyl derivative 9. Compound 7 was synthesized by N1‐alkylation of the corresponding uracil. Significant activity was found against HIV‐1 except for compounds with ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4665186 Thu, 31 Mar 2011 23:00:00 +0100 4665186 http://www.medworm.com/index.php?rid=4627727&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000218 AbstractA new series of 4‐hydroxycoumarin derivatives 3a–d was synthesized by the reaction of 3‐bromo‐4‐hydroxy coumarin 1 with various heteroaldehydes 2a–d in good yields. The synthesized compounds were characterized on the basis of their elemental and spectral (IR, 1H‐NMR and mass spectrometry) analysis. All target compounds were evaluated for their in‐vitro antimicrobial activity against Streptococcus pyogenes, methicillin‐resistant Staphylococcus aureus, Pseudomonas aeruginosa, Klebsiella pneumonia, and Escherichia coli bacterial strains and fungal cultures of Candida albicans, Aspergillus fumigatus, Trichophyton mentagrophytes, and Penicillium marneffei by disk diffusion assay with slight modifications. The minimum inhibitory concentration (MIC) was determined for th... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4627727 Thu, 24 Mar 2011 00:00:00 +0100 4627727 http://www.medworm.com/index.php?rid=4627726&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000304 AbstractTwo series of chlorinated benzhydryl imidazole and triazole derivatives were synthesized and tested in vitro against representative strains of potent pathogenic bacteria (Staphylococcus aureus CIP 4.83, Escherichia hirae CIP 5855, Pseudomonas aeruginosa CIP 82118, Escherichia coli CIP 53126) and fungi (Aspergillus niger IP 1431.83, Candida albicans IP 48.72, Candida krusei IP 208.52, Trichophython rubrum IP 1657.86). Most of these compounds were devoid of any antimicrobial activity, but several of them inhibited T. rubrum with MIC values in the range of 0.125 to 32 µg/mL, similar or superior to those of bifonazole and clotrimazole, used as standard controls. The replacement of the imidazole ring with a triazole moiety in these compounds led to derivatives with less antifungal ac... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4627726 Thu, 24 Mar 2011 00:00:00 +0100 4627726 http://www.medworm.com/index.php?rid=4627725&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000326 AbstractA series of rhodanine‐containing sorafenib analogs was designed, synthesized and evaluated for their in‐vitro antitumor activity against three cancer cell lines (A549, H460 and HT29). Pharmacological data indicated that some of the target compounds possessed marked antiproliferative activity superior to the reference drug sorafenib, especially the most promising compound 7r (with the IC50 value of 0.8, 1.3 and 2.8 µM against A549, H460 and HT29 cell lines, respectively). The activity was found to strongly depend on the substitution pattern of the rhodanine motif at C‐5″ position. Results suggested that this series of compounds could serve as the bases for the development of novel antitumor agents.A series of rhodanine‐containing sorafenib analogs was designed, synthesi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4627725 Thu, 24 Mar 2011 00:00:00 +0100 4627725 http://www.medworm.com/index.php?rid=4665185&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000227 AbstractFused triazolothienopyrimidines were prepared from the corresponding 2‐amino‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carbonitrile. These precursors were intern prepared by employing the Gewald's reaction. All the newly synthesized compounds were characterized by spectral and analytical data. Title compounds displayed promising antibacterial and antifungal activities. Compound 3h which exhibited good antimicrobial activity was incorporated into SLN and characterized for particle size, entrapment efficiency (EE%), scanning electron microscopy (SEM), differential scanning calorimetry (DSC) and in‐vitro release studies. It showed narrow particle size distribution with high entrapment efficiency. In‐vitro release study of compound loaded SLNs in phosphate buffer of pH 7.4, e... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4665185 Tue, 01 Mar 2011 00:00:00 +0100 4665185 http://www.medworm.com/index.php?rid=4627724&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000233 This study examines the synthesis and antibacterial activities of 5,7‐dihydroxycoumarin derivatives, whose structures were confirmed using analytical and spectral data. Twenty compounds were tested for their antibacterial activities against five microbial species such as E. coli, S. aureus, K. pneumonia, P. aeruginosa, and S. typhimurium were studied. Compounds 5 and 12 exhibited the most potent activity against Staphylococcus aureus with a MIC value of 2.5 µg/mL for each of the compounds.This study examines the synthesis and antibacterial activities of 5,7‐dihydroxycoumarin derivatives. Compounds 5 and 12 were the most potent inhibitors against Staphylococcus aureus among tested derivatives with a MIC value of 2.5µg/mL for each of the compounds. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4627724 Tue, 01 Mar 2011 00:00:00 +0100 4627724 http://www.medworm.com/index.php?rid=4555183&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190002 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4555183 Tue, 01 Mar 2011 00:00:00 +0100 4555183 http://www.medworm.com/index.php?rid=4473683&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000194 AbstractA series of 1‐aryl‐3‐isopropylamino‐1‐propanone hydrochlorides 1 and a related heterocyclic analog 2 as candidate antineoplastic agents were prepared and the rationale for designing these compounds is presented. A specific objective in this study is the discovery of novel compounds possessing growth‐inhibiting properties of hepatoma cells. The compounds in series 1 and 2 were prepared and their structures established unequivocally. X‐ray crystallography of two representative compounds 1d and 1g were achieved. Over half of the compounds are more potent than 5‐fluorouracil which is an established drug used in treating liver cancers. QSAR evaluations and molecular modeling studies were undertaken with a view to detecting some physicochemical parameters which govern cyt... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4473683 Mon, 14 Feb 2011 00:00:00 +0100 4473683 http://www.medworm.com/index.php?rid=4473682&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000302 AbstractAldose reductase (ARL2) is the first enzyme in the polyol pathway which catalyzes the NADPH‐dependent reduction of glucose to sorbitol. Its involvement on diabetic complications makes this enzyme a challenge therapeutic target widely investigated to limit and/or prevent them. On this basis, a limited series of 4‐spiro‐oxazolidinone‐benzopyran derivatives (1–7) were synthesized to evaluate them as potential ARL2 inhibitors. The activity was determined spectrophotometrically by monitoring the oxidation of NADPH catalyzed by ALR2. Within the series of compounds, the 4‐methoxy derivative 1b showed to be the most active compound, exhibiting inhibitory levels in the submicromolar range. In addition, the activity against the aldehyde reductase isoform (ARL1) was also evaluated... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4473682 Mon, 14 Feb 2011 00:00:00 +0100 4473682 http://www.medworm.com/index.php?rid=4425254&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000029 AbstractWe have developed a NMR data quantitative structure‐activity relationship NMR‐QSAR model based on 1H‐ and 13C‐NMR experimental spectral data of 4‐(5‐arylamino‐1,3,4‐thiadiazol‐2‐yl)benzene‐1,3‐diols. Compounds show in‐vitro antiproliferative activity against some human cancer cell lines. Two‐parameter equations obtained by the multiple linear regression procedure showed that chemical shifts of the protons of hydroxyl groups and carbon atoms of the 1,3,4‐thiadiazole ring are the decisive descriptors of inhibition interactions of the compounds. The models gave leave‐one‐out (LOO) cross‐validation ranges from 78% to 93%. The obtained NMR‐QSAR equations provide a rapid, reliable, and simple way for predicting the antiproliferative activity of N‐s... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4425254 Wed, 02 Feb 2011 00:00:00 +0100 4425254 http://www.medworm.com/index.php?rid=4425253&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000069 AbstractA series of cis‐restricted 4,5‐diaryl‐3‐aminopyrazole derivatives were synthesized and tested for their cytotoxic activity in vitro against five human cancer cell lines (K562, ECA‐109, A549, SMMC‐7721, and PC‐3). Compounds 5a, 5b, 5d, and 6b showed potent cytotoxicity against all tested cell lines. Primary mechanism research on compound 5a indicated that it was a potent inhibitor of tubulin polymerization, arresting cell cycle in G2/M phase. The docking research showed the conformation of 5a overlaps well with CA‐4 in the crystallized protein complex, suggesting the 4,5‐diaryl‐3‐aminopyrazoles were good mimics of CA‐4.A series of cis‐restricted 4,5‐diaryl‐3‐aminopyrazoles (5a–g, and 6a–f) have been synthesized and evaluated for their biological a... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4425253 Wed, 02 Feb 2011 00:00:00 +0100 4425253 http://www.medworm.com/index.php?rid=4473681&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.200900168 AbstractFive groups of previously synthesized and initially screened non‐substituted and 4‐halogenated arylpiperazin‐1‐yl‐ethyl‐benzimidazoles were estimated for their in‐vitro binding affinities at the rat D2, 5‐HT2A, and α1‐adrenergic receptors. Among all these compounds, 2‐methoxyphenyl and 2‐chlorophenyl piperazines demonstrate the highest affinities for the tested receptors. The effects of 4‐halogenation of benzimidazoles reveal that substitution with bromine may greatly increase the affinity of the compounds for the studied receptors, while the effect of substitution with chlorine is less remarkable. Most of the tested components show 5‐HT2A/D2 pKi binding ratios slightly above or less than 1, while only 4‐chloro‐6‐(2‐{4‐[3‐(trifluoromethyl)phen... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4473681 Tue, 01 Feb 2011 00:00:00 +0100 4473681 http://www.medworm.com/index.php?rid=4461054&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000282 Abstract5‐Arylisoxazolidin‐3‐yl‐3‐diethoxyphosphonates have been synthesized from N‐methyl‐C‐diethoxyphosphorylnitrone and vinyl aryls in good yields and their transformation into the respective phosphonic acids has been accomplished via dealkylation procedure using trimethylsilyl bromide. Phosphonates having 1‐ and 2‐naphthyl substituents at C5 in the isoxazolidine ring as well as the respective phosphonic acids have been found cytotoxic to HeLa and K562 cells with IC50 in the 0.1–0.3 mM range. Preliminary studies on mechanism of action imply that intercalation to DNA is not responsible for their cytotoxic properties.Phosphonates having 1‐ and 2‐naphthyl substituents have been found cytotoxic to HeLa and K562 cells with IC50 in the 0.1–0.3mM range. (Source: A... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4461054 Tue, 01 Feb 2011 00:00:00 +0100 4461054 http://www.medworm.com/index.php?rid=4425255&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190001 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4425255 Tue, 01 Feb 2011 00:00:00 +0100 4425255 http://www.medworm.com/index.php?rid=4425252&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000096 AbstractSome (E/Z)‐aminocarbonyl arylvinylbenzamides (B1–B15) were synthesized, evaluated for anti‐inflammatory activity and ulcerogenic tendency, and their effect on gastro‐intestinal motility in the rats was studied. These benzamides comprising of aliphatic unsaturated region situated between two amide linkages were synthesized by nucleophilic ring opening of appropriate azlactones (AZ1–AZ4) by suitable amines. The characterization of newly synthesized benzamides was performed by IR, 1H‐ and 13C‐NMR, mass and elemental analysis. Amongst the tested compounds, benzamide B1, B2, B4, B5, and B13 were able to produce comparable or superior anti‐inflammatory activity at 10 and 20 mg/kg p.o. dose with respect to standard diclofenac in carrageenan induced rat paw edema model wi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4425252 Tue, 01 Feb 2011 00:00:00 +0100 4425252 http://www.medworm.com/index.php?rid=4356537&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000252 AbstractThe synthesis of new 2‐carboxymethylsulfanylmethyl‐1H‐benzimidazole and 1,3‐dihydro‐4H‐benzo[4′,5′]imidazo[2,1‐c][1,4]thiazine‐4‐one‐8‐carboxylic acid derivatives was investigated. The antiviral activity of compounds 1–14 was tested against the herpes simplex virus 1. Compounds 5 and 14 showed potent activity as they inhibited virus propagation by 94.7% and 91.3% at a dose of 50 µg, respectively. Compounds 5 and 14 showed higher potency than Acyclovir at doses of 20 µg and 50 µg.Novel benzimidazo[2,1‐c][1,4]thiazinone derivatives were synthesized and tested againt the herpes simplex virus 1. Two compounds showed potent activity as they inhibited virus propagation by 94.7% and 91.3% at a dose of 50µg, respectively. (Source: Archiv der Pharmazi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4356537 Mon, 17 Jan 2011 00:00:00 +0100 4356537 http://www.medworm.com/index.php?rid=4356536&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000259 AbstractBased on a novel lead compound 4‐methylpiperazine‐1‐carbodithioic acid 3‐cyano‐3,3‐diphenylpropyl ester 1, the systematic structural modification was carried out. All the synthesized compounds were evaluated for their in‐vitro anticancer activities on four to six different cell lines at three different concentrations. Most of the tested compounds could selectively inhibit the growth of HL‐60 and Bel‐7402 cell lines at a medium concentration. Four compounds (3f, 3g, 3n, and 5) were selected for the IC50 test, and the results revealed that three compounds (3g, 3n, and 5) showed almost the same or a slightly weaker activity than compound 1 against HL‐60, and three compounds (3f, 3g, and 3n) showed >2‐fold higher potency than compound 1 against Bel‐7402. The ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4356536 Mon, 17 Jan 2011 00:00:00 +0100 4356536 http://www.medworm.com/index.php?rid=4356535&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000177 AbstractA new series of 1,4‐bis[5‐(5‐mercapto‐1,3,4‐oxadiazol‐2‐yl‐methyl)‐thio‐4‐substituted‐1,2,4‐triazol‐3‐yl]‐butane 7‐12 and 1,4‐bis[5‐(1‐oxo‐1‐(3,5 dimethyl pyrazol‐1‐yl)‐methyl)‐thio‐4‐substitued‐1,2,4‐triazol‐3‐yl]‐butane 13‐18 were prepared from 1,4‐bis(5[hydrazinocarbonylmethylthio]‐4‐substituted‐1,2,4‐triazol‐3‐yl) butane based derivativess were synthesized 1‐6. All the synthesized compounds were characterized by IR, NMR and Mass spectral studies. The synthesized compounds 7‐18 were screened for in‐vitro cytotoxicity potential using the standard MTT (3‐(4,5‐dimethylthiazol‐2‐yl)‐2,5‐diphenyltetrazolium bromide) assay against a panel of three human cancer cell lines: Lung carcinoma... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4356535 Mon, 17 Jan 2011 00:00:00 +0100 4356535 http://www.medworm.com/index.php?rid=4344305&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000228 AbstractNew compounds of 2‐aryl‐4H‐3,1‐benzothiazine set were synthesized and tested for their antiproliferative activity as part of our research in the antitumor field. The title compounds were obtained by the reaction of aryl‐modified sulfinylbis((2,4‐dihydroxyphenyl)methanethione) with 2‐aminobenzyl alcohols. The reaction proceeded through thiobenzanilide intermediates, which were converted to the 4H‐3,1‐benzothiazine fused ring by an endocyclization process. The structures of compounds were identified from elemental, IR, 1H‐NMR, 13C‐NMR, and MS spectra analyses. The cytotoxicity in vitro against four human cancer cell lines was determined. The antiproliferative properties of some compounds were more beneficial than cisplatin studied comparatively.A new series of 2... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4344305 Fri, 14 Jan 2011 00:00:00 +0100 4344305 http://www.medworm.com/index.php?rid=4415521&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.200900291 AbstractA series of novel 2‐(1H‐benzimidazol‐2‐ylsulfanyl)‐N‐(4‐oxo‐2‐phenyl‐thiazolidin‐3yl)‐acetamide 5a–j have been synthesized from various aldehydes and 2‐(5‐phenyl‐[1,3,4]‐oxadiazol‐2‐ylmethylsulfanyl)‐1H‐benzimidazole 6a–j from various benzoic acids. These compounds were screened for their in‐vitro anti‐bacterial activity against Staphylococcus aureus and Enterococcus faecalis as Gram positive, Klebsiella pneumoniae and Escherichia coli as Gram negative bacterial strains and for in‐vitro anti‐fungal activity against Asperigillus fumigatus and Candida albicans. The in vitro cytotoxic properties were studied using brine shrimp bioassay. Results revealed that, compounds 5b, 5d, 5g, 5i, 6b, 6e, 6f, and 6i showed excellent activity agai... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4415521 Sat, 01 Jan 2011 00:00:00 +0100 4415521 http://www.medworm.com/index.php?rid=4356534&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000172 AbstractIn the present study a new series of benzimidazole derivatives bearing various (benz)azolylthio moieties were synthesized so as to investigate their antimicrobial activity. Structures of the target compounds (5a–5i) were confirmed by their IR, 1H‐NMR, ES‐MS spectral data, and elemental analyses. The synthesized compounds (5a–5i) exhibited poor activity against bacterial strains. On the other hand, antifungal activity of the compounds against Candida species was very significant. Brine‐Shrimp lethality assay was performed for determination of toxicity of the compounds. Compounds 5a, 5c, and 5d were evaluated as non‐toxic in addition to their attractive antifungal activity. However, the other compounds (5b, e–i) in the series showed toxicity to different extents.A new s... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4356534 Sat, 01 Jan 2011 00:00:00 +0100 4356534 http://www.medworm.com/index.php?rid=4344304&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000237 In conclusion, Schiff base transition metal complexes induce strong inhibitory effects on human lymphoma and leukemia cells.Similar but still different – dependent on the transition metal and the ligand structure: Iron salophene and saldach complexes induce various cellular changes such as inhibition of cell growth, induction of apoptosis and release of Cu/Zn superoxide dismutase, a cellular repair enzyme, in human lymphoma and leukemia cell lines. Manganese salophene complexes inhibit only cell growth and free ligands are almost ineffective. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4344304 Sat, 01 Jan 2011 00:00:00 +0100 4344304 http://www.medworm.com/index.php?rid=4319329&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201190000 (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4319329 Sat, 01 Jan 2011 00:00:00 +0100 4319329 http://www.medworm.com/index.php?rid=4295989&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000165 Abstract2‐(2‐Cyano‐acetylamino)‐4,5,6,7‐tetrahydrobenzo[b]thiophene‐3‐carboxylic acid ethyl ester (2) was utilized as a key intermediate for the synthesis of thiocarbamoyl derivative 3via its reaction with phenyl isothiocyanate. Treatment of 3 with chloroacetyl chloride afforded thiazolidin‐5‐one 4. Compound 7 reacted with different α‐halo carbonyl compounds to give thiazolidine 8a,b, and thiazolidin‐4‐one derivatives 9. Treatment of 4 with the appropriate aromatic aldehyde and tolyl diazonium chloride afforded the corresponding thiazolidin‐5‐one derivatives 5a,b and 6, respectively. The thiazolidin‐4‐one derivative 10 was obtained via the reaction of compound 2 with 2‐mercaptoacetic acid. Finally, the thiazoline 11 was obtained via the reaction of compou... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4295989 Mon, 27 Dec 2010 00:00:00 +0100 4295989 http://www.medworm.com/index.php?rid=4295988&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000057 AbstractSynthesis of a new series of 1H‐pyrazole‐1‐carboxamide derivatives is described. Their antiproliferative activity against A375 human melanoma cell line was tested and the effect of substituents on the diarylpyrazole scaffold was investigated. The pharmacological results indicated that most of the newly synthesized compounds showed moderate activity against A375, compared with sorafenib. Among all of these derivatives, compound IIe which has N‐methylpiperazinyl and phenolic moieties showed the most potent antiproliferative activity against A375 human melanoma cell line.A new series of 3,4‐diaryl‐1H‐pyrazole‐1‐carboxamide derivatives was synthesized. Compound IIe having m‐hydroxyphenyl substituted N‐methylpiperazinyl moieties showed the most potent antiprolifera... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4295988 Mon, 27 Dec 2010 00:00:00 +0100 4295988 http://www.medworm.com/index.php?rid=4282282&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000245 AbstractChalcones of 2a–f and their corresponding products, pyrazolines 3a–f, were synthesized and evaluated for their anti‐inflammatory activity against carrageenan edema in albino rats at a dose of 10 mg/kg. All the compounds of this series showed promising anti‐inflammatory activity. The most active compounds of this series, 2a, 2b, and 2d, were found to be most potent. They showed higher percentage of inhibition of edema than the standard drug indomethacin.A new series of chalcones and pyrazoline derivatives was synthesized carrying a morpholinophenyl moiety and their possible anti‐inflammatory activities were investigated. The most potent compounds of this series 2a, 2b, and 2d showed higher percentage of edema inhibition compared to indomethacin. (Source: Archiv der Pharm... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282282 Wed, 22 Dec 2010 00:00:00 +0100 4282282 http://www.medworm.com/index.php?rid=4282281&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000241 AbstractSynthesis, physicochemical and anticonvulsant properties of new N‐Mannich bases 3–24 derived from 5‐cyclopropyl‐5‐phenyl‐ and 5‐cyclopropyl‐5‐(4‐chlorophenyl)‐hydantoins were described here. Initial anticonvulsant screening was performed using intraperitoneal (i.p.) maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) seizures tests. Selected derivatives were also screened in the 6‐Hz test. The neurotoxicity was determined applying the rotorod test. The pharmacological results revealed that the majority of compounds were effective in MES and/or scPTZ tests. The quantitative studies after oral administration into rats showed that several molecules were more potent than phenytoin and ethosuximide which were used as reference antiepileptic dru... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282281 Wed, 22 Dec 2010 00:00:00 +0100 4282281 http://www.medworm.com/index.php?rid=4282280&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000236 AbstractStarting from tadalafil as a template, a series of functionalized tetrahydro‐β‐carboline derivatives have been prepared and identified as novel potent and selective PDE5 inhibitors. Replacing the 3,4‐methylenedioxyphenyl at position 6 of tadalafil, together with elongation of the N2‐methyl substituent and manipulation of the stereochemical aspects of the two chiral carbons led to the identification of compound XXI, a highly potent PDE5 inhibitor (IC50 = 3 nM). Compound XXI was also highly selective for PDE5 versus PDE3B, PDE4B, and PDE11A, with a selectivity index of 52 and 235 towards PDE5 rather than PDE11 with both cAMP and cGMP as substrate, respectively.PDE5 has been successfully targeted for treatment of male erectile dysfunction. Herein we report the synthesis o... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282280 Wed, 22 Dec 2010 00:00:00 +0100 4282280 http://www.medworm.com/index.php?rid=4282279&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000209 AbstractNon‐steroidal anti‐inflammatory drugs (NSAIDs) and antioxidant therapy might protect against the development of Alzheimer's disease (AD). In the present work, we synthesized a molecular combination of glutathione (GSH) and ibuprofen (IBU) via an amide bond and investigated its potential for targeted delivery of the parent drugs to neurons, where cellular oxidative stress and inflammation are related to AD. Evaluation of its physicochemical and in‐vitro antioxidant properties indicated that compound 1 exhibits good stability toward human plasma enzymatic activity, and, like GSH, displays in‐vitro free radical scavenging activity in a time and concentration‐dependent manner. The new compound was also assessed by infusion in a rat model for Alzheimer's disease for its potent... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282279 Wed, 22 Dec 2010 00:00:00 +0100 4282279 http://www.medworm.com/index.php?rid=4282278&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000188 AbstractSynthesis and evaluation of anticancer and antimicrobial activity of some novel pyrazolopyrimidines and fused pyrazolopyrimidines are reported. Twelve analogs were selected to be evaluated for their in vitro anticancer potential against a panel of three human tumor cell lines: hepatocellular carcinoma HepG2, cervical carcinoma HelaS3 and colon carcinoma CaCo. The obtained data revealed that eight compounds namely; 6b, 6d, 7c, 8c, 10b, 12b, 13a and 13b were able to exhibit variable degrees of anticancer activities against the three used cell lines, of which compound 6d proved to be the most active. On the other hand, all the newly synthesized compounds were subjected to in vitro antibacterial and antifungal screening. Almost all the tested compounds were found to possess variable de... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282278 Wed, 22 Dec 2010 00:00:00 +0100 4282278 http://www.medworm.com/index.php?rid=4282277&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000182 Abstract3,5‐Dimethyl‐5‐(4‐pyridyl)hydantoin (L) and its platinum(II) and platinum(IV) complexes with the general formula cis‐[PtL2X2] · n H2O and [PtL2Cl4], where XCl, I and n = 2‐4 were synthesized. A new Pt(IV) complex with 5‐methyl‐5‐(4‐pyridyl)hydantoin (L′) with the formula cis‐[Pt(L′)2Cl2(OH)2] · 5 H2O was also synthesized. The novel compounds were characterized by elemental analysis, IR, 1H‐, 13C‐, 195Pt‐NMR spectra and molar conductivity. The cytotoxic effects of these complexes were examined on three human tumor cell lines by MTT‐dye reduction assay. These four new Pt(II) and Pt(IV) complexes and a set of another twelve Pt(II), Pt(IV), and Pd(II) complexes previously synthesized and tested were compiled and a QSAR model was derive... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282277 Wed, 22 Dec 2010 00:00:00 +0100 4282277 http://www.medworm.com/index.php?rid=4282276&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000167 AbstractRecently, heterocyclic benzimidazole derivatives have been investigated and validated as a promising class of antiviral agents. In this paper, a series of novel thiazolylbenzimidazole derivatives was synthesized and evaluated for their anti‐hepatitis B virus (HBV) activity and cytotoxicity on the HepG2.2.15 cell line. Afterwards, the preliminary structure–activity relationship (SAR) was discussed. Compound 8b, with IC50 = 1.1 µM and SI > 90.9, was the most promising compound and could be selected as a benchmark compound for further investigation.A series of novel benzimidazole analogues was prepared and assessed for their anti‐HBV activity and cytotoxicity in vitro. The preliminary structure–activity relationship (SAR) was discussed. Compound 8b showed good an... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282276 Wed, 22 Dec 2010 00:00:00 +0100 4282276 http://www.medworm.com/index.php?rid=4282275&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000045 AbstractA series of ethyl 6‐bromo‐8‐hydroxyimidazo[1,2‐a]pyridine‐3‐carboxylate derivatives were synthesized and evaluated for their anti‐hepatitis B virus (HBV) activity and cytotoxicity in HepG2.2.15 cells. Nearly half of the tested compounds were proved to be highly effective in inhibiting the replication of HBV DNA with IC50 values ranging from 1.3 to 9.1 µM. Among them, 10o and 10s were identified as the most promising compounds.Hepatitis B is a potentially life‐threatening liver infection caused by the hepatitis B virus. To develop novel anti‐HBV agents, ethyl 6‐bromo‐8‐hydroxyimidazo[1,2‐a]pyridine‐3‐carboxylate derivatives were synthesized and evaluated for their anti‐hepatitis B virus activity and cytotoxicity. (Source: Archiv der Pharmazie) Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282275 Wed, 22 Dec 2010 00:00:00 +0100 4282275 http://www.medworm.com/index.php?rid=4282274&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000010 AbstractA new series of 32 derivatives of 4‐pyrazolyl‐N‐(hetero)arylquinoline 5a–p and 6a–p were synthesized by a one‐pot base‐catalyzed cyclocondensation reaction of 1‐phenyl‐3‐(hetero)aryl‐pyrazole‐4‐carbaldehyde 1a–h, malononitrile 2, and 3‐(hetero)aryl‐5,5‐disubstitutedcyclohex‐2‐enone 3a–b or 4a–b, respectively. All the synthesized compounds were characterized by elemental analysis, FT‐IR, 1H‐NMR, and 13C‐NMR spectral data. All the synthesized compounds were screened, against six bacterial pathogens, namely Bacillus subtilis, Clostridium tetani, Streptococcus pneumoniae, Salmonella typhi, Vibrio cholerae, Escherichia coli, and antifungal activity, against two fungal pathogens Aspergillus fumigatus and Candida albicans, using broth microd... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282274 Wed, 22 Dec 2010 00:00:00 +0100 4282274 http://www.medworm.com/index.php?rid=4282273&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000013 AbstractA series of 5‐nitroimidazole‐based 1,3,4‐thiadiazoles were prepared and tested for antibacterial activity against Helicobacter pylori. The anti‐H. pylori activity of target compounds along with the commercially available antimicrobial metronidazole was evaluated by comparing the inhibition‐zone diameters determined by the paper disc diffusion bioassay. From our bioassay results against 20 clinical isolates it is evident that piperazinyl, 4‐methylpiperazinyl, 3‐methylpiperazinyl, and 3,5‐dimethylpiperazinyl analogs (6a, 6b, 6e, and 6f, respectively) and pyrrolidine derivative 7 had strong activity at 0.5 µg/disc (average of inhibition zone >20 mm) while metronidazole had no activity at this dose. Compound 6f containing the 3,5‐dimethylpiperazinyl moiety at ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4282273 Wed, 22 Dec 2010 00:00:00 +0100 4282273 http://www.medworm.com/index.php?rid=4201146&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000105 AbstractNaproxen is one of the most potent NSAIDs and plays an important role in the treatment of neurodegenerative diseases. Poor brain delivery of naproxen at therapeutic doses, in addition to its serious gastrointestinal side effects, has prompted research into the development of a specific carrier system that is capable of delivering naproxen to the brain at smaller doses. The purpose of this study was to evaluate two brain‐specific carrier systems of naproxen. The first was the dihydropyridine/pyridinium redox system that utilized a lipophilic chemical delivery system coupled to the carboxylic acid group of naproxen through an ethanolamine linker. Secondly, an ascorbic acid system, which has reducing properties and acts as a biological carrier through sodium‐dependent vitamin‐C ... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201146 Thu, 25 Nov 2010 00:00:00 +0100 4201146 http://www.medworm.com/index.php?rid=4201145&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000091 AbstractFatty acid mimetics such as pirinixic acid (PA) derivatives and 2‐(phenylthio)alkanoic acid derivatives are drug‐like small molecules with an interesting pharmacological profile. Previously, we have characterized PA derivatives (e.g., 1) as dual agonists of peroxisome proliferator‐activated receptors (PPARs) α and γ and as inhibitors of microsomal prostaglandin E2‐synthase‐1 (mPGES‐1) and 5‐lipoxygenase (5‐LO). 2‐(Phenylthio)alkanoic acids (e.g., 2) were shown to act as highly active and selective PPARα agonists. Encouraged by these results, we would like to identify other target proteins and, thereby, further explore the pharmacological profile of these molecules. An elegant method to screen for potential interaction partners is the so‐called “protein‐fi... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201145 Thu, 25 Nov 2010 00:00:00 +0100 4201145 http://www.medworm.com/index.php?rid=4201144&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000181 AbstractStevioside, an ent‐kaurene type of diterpenoid glycoside, is a natural sweetener extracted from leaves of Stevia rebaudiana (Bertoni) Bertoni. Stevioside and a few related compounds are regarded as the most common active principles of the plant. Such phytochemicals have not only been established as non‐caloric sweeteners, but reported to exhibit some other pharmacological activities also. In this article, natural distribution of stevioside and related compounds, their structural features, plausible biosynthetic pathways along with an insight into the structure–sweetness relationship are presented. Besides, the pharmacokinetics, wide‐range of pharmacological potentials, safety evaluation and clinical trials of these ent‐kaurene glycosides are revisited.Stevioside and relat... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201144 Thu, 25 Nov 2010 00:00:00 +0100 4201144 http://www.medworm.com/index.php?rid=4201143&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000201 AbstractThiosemicarbazones of p‐aminobenzoic acid (PABA) were synthesized and tested for their antimicrobial and anticancer activity. Hydroxamate derivatives 4a–4l were found to have better antimicrobial and anticancer activity than their acid counterpart. Compound 4d was found to have good antimicrobial activity against Escherichia coli, Klebsiella pneumoniae, Staphylococcus aureus, Vibrio cholerae, and Bacillus subtilis with IC50 value of about 1 µM. Compound 4f showed potent antifungal activity against Candida albicans (IC50 = 1.29 µM) and compound 4h showed potent anticancer activity (IC50 = 0.07 µM).Hydroxamate derivatives 4a–4l were found to show better antimicrobial and anticancer activity in compariosn with their acid counterpart 3a–3l. (Source: Archiv der Pharma... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201143 Thu, 25 Nov 2010 00:00:00 +0100 4201143 http://www.medworm.com/index.php?rid=4201142&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000148 AbstractAgelasines are 7,9‐dialkylpurinium salts found in marine sponges (Agelas sp.), which display a variety of antimicrobial and cytotoxic effects. We have synthesized simplified agelasine analogs modified in the purine 2‐position and examined their antimicrobial and anticancer activities. The compounds were screened against Staphylococcus aureus, Escherichia coli, Mycobacterium tuberculosis, Candida krusei, and Candida albicans, protozoa causing tropical diseases (Plasmodium falciparum, Leishmania infantum, Trypanosoma cruzi, and Trypanosoma brucei), a panel of human cancer cell lines (U‐937 GTB, RPMI 8226/s, CEM/s, and ACHN) as well as VERO and/or MRC‐5 cells. The results indicate that the introduction of a methyl group in the purine 2‐position is beneficial for antimycobact... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201142 Thu, 25 Nov 2010 00:00:00 +0100 4201142 http://www.medworm.com/index.php?rid=4201141&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000147 AbstractThis experiment was designed to synthesize 18 kinds of polyhydroxybenzophenones by using Friedel‐Crafts reaction, and to measure the inhibitory activity on α‐glucosidase with p‐nitrophenyl‐β‐D‐galactopyranoside (PNPG) as a substrate. Here, acarbose (IC50 = 1674.75 µmol L−1) was used as the reference inhibitor. The results demonstrated that most of the target compounds had remarkable inhibitory activities on α‐glucosidase. Among all these compounds, 2,4,4′,6‐butahydroxydiphenylketone (11) was found to be the most potent α‐glucosidase inhibitor with an IC50 value of 10.62 µmol L−1. In addition, we found these compounds were competitive inhibitors through the kinetic analysis. The results suggested that such compounds might be utilized for the... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201141 Thu, 25 Nov 2010 00:00:00 +0100 4201141 http://www.medworm.com/index.php?rid=4201140&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000098 AbstractA series of (Z)‐2‐(substituted aryl)‐N‐(3‐oxo‐4‐(substituted carbamothioyl)‐3,4‐dihydro‐2H‐benzo[b][1,4]oxazin‐7‐yl) hydrazine carboxamides (6a–r) was synthesized using 2‐amino‐5‐nitrophenol as a starting material. All the synthesized compounds possessed two hydrogen‐bonding domains and their effect on the activity was studied thereof. The anticonvulsant activity was assessed by the maximal electroshock test (MES), subcutaneous pentylenetetrazole test (scPTZ) and intraperitoneal thiosemicarbazide test (ipTSC). Compounds (6b, 6h, 6i, and 6p) were found to be the most potent of the series as they showed 83–100% protection in the MES test. They also displayed considerable activity in the chemically induced seizure tests. Most of the tested compoun... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201140 Thu, 25 Nov 2010 00:00:00 +0100 4201140 http://www.medworm.com/index.php?rid=4201139&cid=s_33585_13_f&fid=33585&url=http%3A%2F%2Fdx.doi.org%2F10.1002%252Fardp.201000088 AbstractA series of novel thiazolo derivatives 2–15 was synthesized by initial condensation of 2,6‐dihydroxyisonicotinohydrazide 1 and 2‐chloro‐6‐hydrazinylisonicotinohydrazide 11 with different organic reagents. The pharmacological screening showed that many of these obtained compounds have good anti‐inflammatory, analgesic, anticonvulsant, and antiparkinsonian activities comparable to diclofenac potassium, Voltarene®, Carbamazepine®, and Benzotropene® as reference drugs. Initially the acute toxicity of the compounds was assayed via the determination of their LD50. The structures of newly synthesized compounds were confirmed by IR, 1H‐NMR, 13C‐NMR, MS spectral data and elemental analysis. The detailed synthesis, spectroscopic data, LD50 and pharmacological activities of... Archiv der Pharmazie journals http://www.medworm.com/rss/comments.php?id=4201139 Thu, 25 Nov 2010 00:00:00 +0100 4201139