Discovery of digallic acid as XOD/URAT1 dual target inhibitor for the treatment of hyperuricemia
Bioorg Chem. 2024 Apr 23;147:107381. doi: 10.1016/j.bioorg.2024.107381. Online ahead of print.ABSTRACTThe development of XOD/URAT1 dual target inhibitors has emerged as a promising therapeutic strategy for the management of hyperuricemia. Here, through virtual screening, we have identified digallic acid as a novel dual target inhibitor of XOD/URAT1 and subsequently evaluated its pharmacological properties, pharmacokinetics, and toxicities. Digallic acid inhibited URAT1 with an IC50 of 5.34 ± 0.65 μM, which is less potent than benzbromarone (2.01 ± 0.36 μM) but more potent than lesinurad (10.36 ± 1.23 μM). Docking and...
Source: Bioorganic Chemistry - April 26, 2024 Category: Chemistry Authors: Fengxin Zheng Suiqing Mai Xiaolin Cen Pei Zhao Wenjie Ye Jiale Ke Shiqin Lin Huazhong Hu Zitao Guo Shuqin Zhang Hui Liao Ting Wu Yuanxin Tian Qun Zhang Jianxin Pang Zean Zhao Source Type: research
Synthesis and evaluation of pentacyclic triterpenoids conjugates as novel HBV entry inhibitors targeting NTCP receptor
In this study, pentacyclic triterpenoids (PTs) including glycyrrhetinic acid (GA), oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) were modified via molecular hybridization with podophyllotoxin respectively, and resulted in thirty-two novel conjugates. The anti-HBV activities of conjugates were evaluated in HepG2.2.15 cells. The results showed that 66% of the conjugates exhibited lower toxicity to the host cells and had significant inhibitory effects on the two HBV antigens, especially HBsAg. Notably, the compounds BA-PPT1, BA-PPT3, BA-PPT4, and UA-PPT3 not only inhibited the secretion of HBsAg but also supp...
Source: Bioorganic Chemistry - April 25, 2024 Category: Chemistry Authors: Yixin Chen Meitao Duan Xiangwan Wang Jianling Xu Shuo Tian Xiaotian Xu Ao Duan Ahmed Mahal Yongyan Zhu Quanhong Zhu Source Type: research
Synthesis and evaluation of pentacyclic triterpenoids conjugates as novel HBV entry inhibitors targeting NTCP receptor
In this study, pentacyclic triterpenoids (PTs) including glycyrrhetinic acid (GA), oleanolic acid (OA), ursolic acid (UA) and betulinic acid (BA) were modified via molecular hybridization with podophyllotoxin respectively, and resulted in thirty-two novel conjugates. The anti-HBV activities of conjugates were evaluated in HepG2.2.15 cells. The results showed that 66% of the conjugates exhibited lower toxicity to the host cells and had significant inhibitory effects on the two HBV antigens, especially HBsAg. Notably, the compounds BA-PPT1, BA-PPT3, BA-PPT4, and UA-PPT3 not only inhibited the secretion of HBsAg but also supp...
Source: Bioorganic Chemistry - April 25, 2024 Category: Chemistry Authors: Yixin Chen Meitao Duan Xiangwan Wang Jianling Xu Shuo Tian Xiaotian Xu Ao Duan Ahmed Mahal Yongyan Zhu Quanhong Zhu Source Type: research
Pyrano[2,3-c]pyrazole fused spirooxindole-linked 1,2,3-triazoles as antioxidant agents: Exploring their utility in the development of antidiabetic drugs via inhibition of α-amylase and DPP4 activity
Bioorg Chem. 2024 Apr 10;147:107363. doi: 10.1016/j.bioorg.2024.107363. Online ahead of print.ABSTRACTEnvironment-benign, multicomponent synthetic methodologies are vital in modern pharmaceutical research and facilitates multi-targeted drug development via synergistic approach. Herein, we reported green and efficient synthesis of pyrano[2,3-c]pyrazole fused spirooxindole linked 1,2,3-triazoles using a tea waste supported copper catalyst (TWCu). The synthetic approach involves a one-pot, five-component reaction using N-propargylated isatin, hydrazine hydrate, ethyl acetoacetate, malononitrile/ethyl cyanoacetate and aryl azi...
Source: Bioorganic Chemistry - April 24, 2024 Category: Chemistry Authors: Sandhya Chahal Payal Rani None Shweta Kapil Kumar Goel Gaurav Joshi Rajvir Singh Parvin Kumar Devender Singh Jayant Sindhu Source Type: research
Design, synthesis, in vitro and in silico evaluations of new isatin-triazine- aniline hybrids as potent anti- Alzheimer multi-target directed lead compounds
In this study, using rational design, we synthesized new 15 hybrids of the s-triazine, isatin and aniline derivatives as anti- AD compounds. The design was as way as that new compounds could had anti cholinesterase (ChE), antioxidant and biometal chelation ability. In vitro biological evaluation against ChE enzymes showed that these molecules were excellent inhibitors with IC50 values ranging from 0.2 nM to 734.5 nM for acetylcholinesterase (AChE), and 0.02 μM to 1.92 μM for butyrylcholinesterase (BChE). Among these compounds, 8 l with IC50 AChE = 0.7 nM, IC50 BChE = 0.09 μM and 8n with IC50 AChE = 0.2 nM, IC50 BChE = 0...
Source: Bioorganic Chemistry - April 24, 2024 Category: Chemistry Authors: Yasaman Tamaddon-Abibigloo Siavoush Dastmalchi Nima Razzaghi-Asl Javid Shahbazi Mojarrad Source Type: research
Synthesis and biological evaluation of Halogen-Substituted novel α-Ketoamides as potential protein aggregation modulators in Alzheimer's disease
In this study, a series of α-ketoamide derivatives was synthesized from β,γ-unsaturated α-keto thioesters, achieving high purity and good yield. Thioflavin T based Aβ aggregation assay identified four promising compounds (BD19, BD23, BD24, and BD27) that demonstrated significant inhibitory effects on Aβ aggregation. BD23, selected for its better solubility (0.045 ± 0.0012 mg/ml), was further subjected to in vitro Parallel Artificial Membrane Permeability Assay to determine the Blood-Brain-Barrier permeability and emerged as BBB permeable with permeability rate (Pe) of 10.66 ± 8.11 × 10-6 cm/s. In addition to its A...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Bhanuranjan Das Anurag Tk Baidya Sourabh Chakrabarti Deepak Chouhan Banita Thakur Taher Darreh-Shori Gefei Chen Vinod Tiwari Rajnish Kumar Source Type: research
Lathyrane and premyrsinane Euphorbia diterpenes against Alzheimer's disease: Bioinspired synthesis, anti-cholinesterase and neuroprotection bioactivity
Bioorg Chem. 2024 Apr 15;147:107377. doi: 10.1016/j.bioorg.2024.107377. Online ahead of print.ABSTRACTThe first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioacti...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Lian Sun Xin-Ming Wang Qianhui Tang Yao Xiao Jin-Bu Xu Tong-Tong Zhang Yan-Jun Liu Xiaohuan Li Feng Gao Source Type: research
Novel 1,3,4-oxadiazole derivatives as highly potent microsomal prostaglandin E < sub > 2 < /sub > synthase-1 (mPGES-1) inhibitors
Bioorg Chem. 2024 Apr 16;147:107383. doi: 10.1016/j.bioorg.2024.107383. Online ahead of print.ABSTRACTSelective inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) is implicated as a new therapeutic modality for the development of new-generation anti-inflammatory drugs. Here, we present the discovery of new and potent inhibitors of human mPGES-1, i.e., compounds 13, 15-25, 29-30 with IC50 values in the range of 5.6-82.3 nM in a cell-free assay of prostaglandin (PG)E2 formation. We also demonstrate that 20 (TG554, IC50 = 5.6 nM) suppresses leukotriene (LT) biosynthesis at low µM concentrations, providing a bench...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Tu ğçe Gür Maz Philipp Dahlke Azize Gizem Erg ül Abdurrahman Ol ğaç Paul M Jordan Burcu Çalışkan Oliver Werz Erden Banoglu Source Type: research
Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations
Bioorg Chem. 2024 Apr 17;147:107372. doi: 10.1016/j.bioorg.2024.107372. Online ahead of print.ABSTRACTJoining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105-130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivat...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Eman R Mohammed Aliaa H Abd-El-Fatah Abdalla R Mohamed Marianne A Mahrouse Mohammad A Mohammad Source Type: research
Biological activity and computational analysis of novel acrylonitrile derived benzazoles as potent antiproliferative agents for pancreatic adenocarcinoma with antioxidative properties
Bioorg Chem. 2024 Apr 6;147:107326. doi: 10.1016/j.bioorg.2024.107326. Online ahead of print.ABSTRACTContinuing our research into the anticancer properties of acrylonitriles, we present a study involving the design, synthesis, computational analysis, and biological assessment of novel acrylonitriles derived from methoxy, hydroxy, and N-substituted benzazole. Our aim was to examine how varying the number of methoxy and hydroxy groups, as well as the N-substituents on the benzimidazole core, influences their biological activity. The newly synthesized acrylonitriles exhibited strong and selective antiproliferative effects aga...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Anja Be č Leentje Persoons Dirk Daelemans Kristina Star čević Robert Vianello Marijana Hranjec Source Type: research
Corrigendum to "Synthesis and preclinical evaluation of a novel molecular probe [ < sup > 18 < /sup > F]AlF-NOTA-PEG < sub > 2 < /sub > -Asp < sub > 2 < /sub > -PDL1P for PET imaging of PD-L1 positive tumor" [Bioorgan. Chem. 145 (2024) 107193]
Bioorg Chem. 2024 Apr 22:107368. doi: 10.1016/j.bioorg.2024.107368. Online ahead of print.NO ABSTRACTPMID:38653603 | DOI:10.1016/j.bioorg.2024.107368 (Source: Bioorganic Chemistry)
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Penghui Sun Chunwei Mo Lu Bai Meng Wang Zihao Chen Meilian Zhang Yanjiang Han Haoran Liang Ganghua Tang Source Type: research
Synthesis and biological evaluation of Halogen-Substituted novel α-Ketoamides as potential protein aggregation modulators in Alzheimer's disease
In this study, a series of α-ketoamide derivatives was synthesized from β,γ-unsaturated α-keto thioesters, achieving high purity and good yield. Thioflavin T based Aβ aggregation assay identified four promising compounds (BD19, BD23, BD24, and BD27) that demonstrated significant inhibitory effects on Aβ aggregation. BD23, selected for its better solubility (0.045 ± 0.0012 mg/ml), was further subjected to in vitro Parallel Artificial Membrane Permeability Assay to determine the Blood-Brain-Barrier permeability and emerged as BBB permeable with permeability rate (Pe) of 10.66 ± 8.11 × 10-6 cm/s. In addition to its A...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Bhanuranjan Das Anurag Tk Baidya Sourabh Chakrabarti Deepak Chouhan Banita Thakur Taher Darreh-Shori Gefei Chen Vinod Tiwari Rajnish Kumar Source Type: research
Lathyrane and premyrsinane Euphorbia diterpenes against Alzheimer's disease: Bioinspired synthesis, anti-cholinesterase and neuroprotection bioactivity
Bioorg Chem. 2024 Apr 15;147:107377. doi: 10.1016/j.bioorg.2024.107377. Online ahead of print.ABSTRACTThe first systematic acylated diversification of naturally scarce premyrsinane diterpenes, together with their biosynthetic precursors lathyrane diterpene were carried out. Two new series of premyrsinane derivates (1a-32a) and lathyrane derivates (1-32) were synthesized from the naturally abundant lathyrane diterpene Euphorbia factor L3 through a bioinspired approach. The cholinesterase inhibitory and neuroprotective activities of these diterpenes were investigated to explore potential anti-Alzheimer's disease (AD) bioacti...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Lian Sun Xin-Ming Wang Qianhui Tang Yao Xiao Jin-Bu Xu Tong-Tong Zhang Yan-Jun Liu Xiaohuan Li Feng Gao Source Type: research
Novel 1,3,4-oxadiazole derivatives as highly potent microsomal prostaglandin E < sub > 2 < /sub > synthase-1 (mPGES-1) inhibitors
Bioorg Chem. 2024 Apr 16;147:107383. doi: 10.1016/j.bioorg.2024.107383. Online ahead of print.ABSTRACTSelective inhibition of microsomal prostaglandin E2 synthase-1 (mPGES-1) is implicated as a new therapeutic modality for the development of new-generation anti-inflammatory drugs. Here, we present the discovery of new and potent inhibitors of human mPGES-1, i.e., compounds 13, 15-25, 29-30 with IC50 values in the range of 5.6-82.3 nM in a cell-free assay of prostaglandin (PG)E2 formation. We also demonstrate that 20 (TG554, IC50 = 5.6 nM) suppresses leukotriene (LT) biosynthesis at low µM concentrations, providing a bench...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Tu ğçe Gür Maz Philipp Dahlke Azize Gizem Erg ül Abdurrahman Ol ğaç Paul M Jordan Burcu Çalışkan Oliver Werz Erden Banoglu Source Type: research
Discovery of new 2-(3-(naphthalen-2-yl)-4,5-dihydro-1H-pyrazol-1-yl)thiazole derivatives with potential analgesic and anti-inflammatory activities: In vitro, in vivo and in silico investigations
Bioorg Chem. 2024 Apr 17;147:107372. doi: 10.1016/j.bioorg.2024.107372. Online ahead of print.ABSTRACTJoining the global demand for the discovery of potent NSAIDs with minimized ulcerogenic effect, new pyrazole clubbed thiazole derivatives 5a-o were designed and synthesized. The new derivatives were initially evaluated for their analgesic activity. Eight compounds 5a, 5c, 5d, 5e, 5f, 5h, 5m, and 5o showed higher activity than Indomethacin (potency = 105-130 % vs. 100 %). Subsequently, they were picked for further evaluation of their anti-inflammatory activity, ulcerogenic liability as well as toxicological studies. Derivat...
Source: Bioorganic Chemistry - April 23, 2024 Category: Chemistry Authors: Eman R Mohammed Aliaa H Abd-El-Fatah Abdalla R Mohamed Marianne A Mahrouse Mohammad A Mohammad Source Type: research
