2,3-Dichloronaphthoquinone derivatives: Synthesis, antimicrobial activity, molecular modelling and ADMET studies
Bioorg Chem. 2024 Mar 20;146:107300. doi: 10.1016/j.bioorg.2024.107300. Online ahead of print.ABSTRACTIn the present study, an intermediate namely 2-(3-bromopropylamino)-3-chloronaphthalene-1,4-dione was initially synthesized via the nucleophilic addition-elimination reaction between 2,3-dichloro-1,4-naphthoquinone and 3-bromo-1-aminopropane. Then a coupling reaction between the intermediate and piperazine derivatives yielded a number of 1,4-naphthoquinone derivatives. Spectroscopic analysis successfully characterized the products that were obtained in good yields. In vitro antibacterial properties of the compounds were ex...
Source: Bioorganic Chemistry - March 24, 2024 Category: Chemistry Authors: Hakan Kolanc ılar Hafize Özcan Ay şen Şuekinci Yılmaz Alparslan Semih Salan Abdulilah Ece Source Type: research

Discovery of potential components characteristic by conjugated enone from the branches and leaves of Croton lauioides with anti-neuroinflammatory activity via regulating the NF- κB pathway
In this study, the chemical composition and pharmacological activity of Croton lauioides were investigated for the first time. The bioactive and HPLC-UV guided isolation led to the discovery of twenty-three conjugated enone-type components (1-23), including nine previously unknown sesquiterpenoid derivatives (1-4, 9-10, 12-14). Notably, compounds 1 and 12 are epoxides containing an endoperoxide bridge (1) or a unique dioxaspiro core (12), respectively. Compounds 2-7 are non-benzenoid aromatics featuring a tropone function, while 9-11 possess a rare rearranged scaffold with tropone shift into benzene. Extensive characteriza...
Source: Bioorganic Chemistry - March 24, 2024 Category: Chemistry Authors: Yue Jin Zongxin Guo Huilin Zhu Zixuan Zhang Xiaowen Jiang Yiren Yang Pengyu Liu Yu Yang Miao Wang Huiyuan Gao Source Type: research

Insights into nucleoside hydrolase from Leishmania donovani inhibition: A new bioaffinity chromatography-based screening assay and docking studies
In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(β-d-Ribofuranosyl)-4-quinolone derivative) ...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: Camila Anchau Wegermann Evelyn Santana Bezerra Isabella Gomes de Macedo Sant'Anna Pamella Christina Ortega De Oliveira Rodrigo da Costa Silva Thamires Rocco Machado Luzineide Wanderley Tinoco Maria Cec ília Bastos Vieira de Souza Pedro Pascutti Fernanda Source Type: research

Modular preparation of biphenyl triazoles via click chemistry as non-competitive hyaluronidase inhibitors
In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6, as well as quinoline-containing triazoles 15 and 16, as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulat...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: Yiman Qin Guanyi Li Ling Wang Guangyuan Yin Xiang Zhang Hongxiang Wang Pengfei Zheng Wentao Hua Yan Cheng Yaxue Zhao Jiong Zhang Source Type: research

Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF- κB pathway
Bioorg Chem. 2024 Mar 21;146:107303. doi: 10.1016/j.bioorg.2024.107303. Online ahead of print.ABSTRACTArylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: Xiaoming Wu Long Zhou Ziyun Li Kuanrong Rong Shan Gao Yun Chen Jiawei Zuo Wenjian Tang Source Type: research

Synthesis of new trypanocidal agents from the hybridisation of metronidazole and eugenol analogues
This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised com...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: M ônica Fraccarolli Pelozo Cleydson Finotti Cordeiro Let ícia Fonseca Inácio Rayssa de Cassia Alves Lemini Elda Gon çalves Souza E Leite Monique Dias Benedetti Cristiane Alves Tulha R ômulo Dias Novaes Ivo Santana Caldas Diogo Teixeira Carvalho Stef Source Type: research

Insights into nucleoside hydrolase from Leishmania donovani inhibition: A new bioaffinity chromatography-based screening assay and docking studies
In this study, LdNH was immobilized into fused silica capillaries, resulting in immobilized enzyme reactors (IMERs). The LdNH-IMER activity was monitored on-flow in a multidimensional liquid chromatography system, with the IMER in the first dimension. A C18 analytical column in the second dimension furnished the rapid separation of the substrate (inosine) and product (hypoxanthine), enabling direct enzyme activity monitoring through product quantification. LdNH-IMER exhibited high stability and was characterized by determining the Michaelis-Menten constant. A known inhibitor (1-(β-d-Ribofuranosyl)-4-quinolone derivative) ...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: Camila Anchau Wegermann Evelyn Santana Bezerra Isabella Gomes de Macedo Sant'Anna Pamella Christina Ortega De Oliveira Rodrigo da Costa Silva Thamires Rocco Machado Luzineide Wanderley Tinoco Maria Cec ília Bastos Vieira de Souza Pedro Pascutti Fernanda Source Type: research

Modular preparation of biphenyl triazoles via click chemistry as non-competitive hyaluronidase inhibitors
In this study, to identify novel hyaluronidase inhibitors, we applied click chemistry for the modular synthesis of 370 triazoles in 96-well plates, starting with biphenyl azide. Utilizing an optimized turbidimetric screening assay in microplates, we identified Fmoc-containing triazoles 5 and 6, as well as quinoline-containing triazoles 15 and 16, as highly effective hyaluronidase inhibitors. Subsequent research indicated that these triazoles potentially interact with a novel binding site of hyaluronidase. Notably, these inhibitors displayed minimal cytotoxicity and showed promising anti-inflammatory effects in LPS-stimulat...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: Yiman Qin Guanyi Li Ling Wang Guangyuan Yin Xiang Zhang Hongxiang Wang Pengfei Zheng Wentao Hua Yan Cheng Yaxue Zhao Jiong Zhang Source Type: research

Arylacryl amides: Design, synthesis and the protection against cisplatin-induced acute kidney injury via TLR4/STING/NF- κB pathway
Bioorg Chem. 2024 Mar 21;146:107303. doi: 10.1016/j.bioorg.2024.107303. Online ahead of print.ABSTRACTArylpropionic ester scaffold was found as anti-inflammatory agents for the treatment and prevention of acute kidney injury (AKI). To further study the structure-activity relationship (SAR) of this scaffold, a series of acryl amides were designed, synthesized, and evaluated their anti-inflammation. Of these, compound 9d displayed the protective effect on renal tubular epithelial cells to significantly enhance the survival rate through inhibiting NF-κB phosphorylation and promoting cell proliferation in cisplatin-induced HK...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: Xiaoming Wu Long Zhou Ziyun Li Kuanrong Rong Shan Gao Yun Chen Jiawei Zuo Wenjian Tang Source Type: research

Synthesis of new trypanocidal agents from the hybridisation of metronidazole and eugenol analogues
This study focuses on synthesising new trypanocidal agents from the hybridisation of metronidazole with different natural phenols (eugenol, dihydroeugenol and guaiacol). Two different coupling methodologies have been explored in order to analyse the influence of the connector on bioactivity: i) classic direct esterification (AD compounds) and ii) "click" chemistry using a triazole connector (AC compounds). The in vitro trypanocidal tests show good results for both AC and AD hybrid compounds against both epimastigote and trypomastigote forms of T. cruzi. In silico studies showed positive data for most of the synthesised com...
Source: Bioorganic Chemistry - March 23, 2024 Category: Chemistry Authors: M ônica Fraccarolli Pelozo Cleydson Finotti Cordeiro Let ícia Fonseca Inácio Rayssa de Cassia Alves Lemini Elda Gon çalves Souza E Leite Monique Dias Benedetti Cristiane Alves Tulha R ômulo Dias Novaes Ivo Santana Caldas Diogo Teixeira Carvalho Stef Source Type: research

Magnolol derivatives as specific and noncytotoxic inhibitors of breast cancer resistance protein (BCRP/ABCG2)
Bioorg Chem. 2024 Mar 16;146:107283. doi: 10.1016/j.bioorg.2024.107283. Online ahead of print.ABSTRACTThe breast cancer resistance protein (BCRP/ABCG2) transporter mediates the efflux of numerous antineoplastic drugs, playing a central role in multidrug resistance related to cancer. The absence of successful clinical trials using specific ABCG2 inhibitors reveals the urge to identify new compounds to attend this critical demand. In this work, a series of 13 magnolol derivatives was tested as ABCG2 inhibitors. Only two compounds, derivatives 10 and 11, showed partial and complete ABCG2 inhibitory effect, respectively. This ...
Source: Bioorganic Chemistry - March 21, 2024 Category: Chemistry Authors: Isadora da Silva Zanzarini Diogo Henrique Kita Gustavo Scheiffer Kelly Karoline Dos Santos Julia de Paula Dutra Matteo Augusto Pastore Fabiane Gomes de Moraes Rego Geraldo Picheth Suresh V Ambudkar Luana Pulvirenti Nunzio Cardullo Vivian Rotuno Moure Vera Source Type: research

Synthesis and preclinical evaluation of < sup > 11 < /sup > C-labeled 7-Oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine radioligands for RIPK1 positron emission tomography imaging
In this study, we present the development and characterization of two new PET radioligands, [11C]PB218 and [11C]PB220, which have the potential to facilitate brain RIPK1 imaging. [11C]PB218 and [11C]PB220 were successfully synthesized with a high radiochemical yield (34 % - 42 %) and molar activity (293 - 314 GBq/µmol). PET imaging characterization of two radioligands was conducted in rodents, demonstrating that both newly developed tracers have good brain penetration (maximum SUV = 0.9 - 1.0) and appropriate brain clearance kinetic profiles. Notably, [11C]PB218 has a more favorable binding specificity than [11C]PB220. A ...
Source: Bioorganic Chemistry - March 21, 2024 Category: Chemistry Authors: Tianwen Luo Na Sang Yan Liu Yanting Zhou Rui Wu Frederick A Bagdasarian Hsiao-Ying Wey Jinyi Lang Changning Wang Ping Bai Source Type: research

Multivalent pyrrolidines acting as pharmacological chaperones against Gaucher disease
Bioorg Chem. 2024 Mar 16;146:107295. doi: 10.1016/j.bioorg.2024.107295. Online ahead of print.ABSTRACTA concise asymmetric synthesis of clickable enantiomeric pyrrolidines was achieved using Crabbé-Ma allenation. The synthesized iminosugars were grafted by copper-free strain-promoted alkyne-azide cycloaddition onto phosphorus dendrimers. The hexavalent and dodecavalent pyrrolidines were evaluated as β-glucocerebrosidase inhibitors. The level of inhibition suggests that monofluorocyclooctatriazole group may contribute to the affinity for the protein leading to potent multivalent inhibitors. Docking studies were carried ou...
Source: Bioorganic Chemistry - March 21, 2024 Category: Chemistry Authors: Marc Borie-Guichot My Lan Tran Virginie Garcia Abdelouahd Oukhrib Fr édéric Rodriguez C édric-Olivier Turrin Thierry Levade Yves G énisson St éphanie Ballereau C écile Dehoux Source Type: research

Magnolol derivatives as specific and noncytotoxic inhibitors of breast cancer resistance protein (BCRP/ABCG2)
Bioorg Chem. 2024 Mar 16;146:107283. doi: 10.1016/j.bioorg.2024.107283. Online ahead of print.ABSTRACTThe breast cancer resistance protein (BCRP/ABCG2) transporter mediates the efflux of numerous antineoplastic drugs, playing a central role in multidrug resistance related to cancer. The absence of successful clinical trials using specific ABCG2 inhibitors reveals the urge to identify new compounds to attend this critical demand. In this work, a series of 13 magnolol derivatives was tested as ABCG2 inhibitors. Only two compounds, derivatives 10 and 11, showed partial and complete ABCG2 inhibitory effect, respectively. This ...
Source: Bioorganic Chemistry - March 21, 2024 Category: Chemistry Authors: Isadora da Silva Zanzarini Diogo Henrique Kita Gustavo Scheiffer Kelly Karoline Dos Santos Julia de Paula Dutra Matteo Augusto Pastore Fabiane Gomes de Moraes Rego Geraldo Picheth Suresh V Ambudkar Luana Pulvirenti Nunzio Cardullo Vivian Rotuno Moure Vera Source Type: research

Synthesis and preclinical evaluation of < sup > 11 < /sup > C-labeled 7-Oxo-2,4,5,7-tetrahydro-6H-pyrazolo[3,4-c]pyridine radioligands for RIPK1 positron emission tomography imaging
In this study, we present the development and characterization of two new PET radioligands, [11C]PB218 and [11C]PB220, which have the potential to facilitate brain RIPK1 imaging. [11C]PB218 and [11C]PB220 were successfully synthesized with a high radiochemical yield (34 % - 42 %) and molar activity (293 - 314 GBq/µmol). PET imaging characterization of two radioligands was conducted in rodents, demonstrating that both newly developed tracers have good brain penetration (maximum SUV = 0.9 - 1.0) and appropriate brain clearance kinetic profiles. Notably, [11C]PB218 has a more favorable binding specificity than [11C]PB220. A ...
Source: Bioorganic Chemistry - March 21, 2024 Category: Chemistry Authors: Tianwen Luo Na Sang Yan Liu Yanting Zhou Rui Wu Frederick A Bagdasarian Hsiao-Ying Wey Jinyi Lang Changning Wang Ping Bai Source Type: research