Synthesis and biological evaluation of triazolones/oxadiazolones as novel urease inhibitors
Bioorg Med Chem. 2024 Feb 25;102:117656. doi: 10.1016/j.bmc.2024.117656. Online ahead of print.ABSTRACTUrease is the main virulence factor of infectious gastritis and gastric ulcers. Urease inhibitors are regarded as the first choice for the treatment of such diseases. Based on the triazolone/oxadiazolone skeleton, a urea-like fragment being able to specifically bind the urease activity pocket and prevent urea from hydrolysis, we designed and synthesized 45 triazolones/oxadiazolones as urease inhibitors. Eight compounds were proved to show excellent inhibitory activity against Helicobacter pylori urease, being more potency...
Source: Bioorganic and Medicinal Chemistry - February 29, 2024 Category: Chemistry Authors: Yi-Ning Wang Su-Ya Li Liang-Chao Yuan Shu-Fang Bu Yao Zeng Zhu-Ping Xiao Hai-Liang Zhu Source Type: research

Synthesis and biological evaluation of triazolones/oxadiazolones as novel urease inhibitors
Bioorg Med Chem. 2024 Feb 25;102:117656. doi: 10.1016/j.bmc.2024.117656. Online ahead of print.ABSTRACTUrease is the main virulence factor of infectious gastritis and gastric ulcers. Urease inhibitors are regarded as the first choice for the treatment of such diseases. Based on the triazolone/oxadiazolone skeleton, a urea-like fragment being able to specifically bind the urease activity pocket and prevent urea from hydrolysis, we designed and synthesized 45 triazolones/oxadiazolones as urease inhibitors. Eight compounds were proved to show excellent inhibitory activity against Helicobacter pylori urease, being more potency...
Source: Bioorganic and Medicinal Chemistry - February 29, 2024 Category: Chemistry Authors: Yi-Ning Wang Su-Ya Li Liang-Chao Yuan Shu-Fang Bu Yao Zeng Zhu-Ping Xiao Hai-Liang Zhu Source Type: research

Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents
Bioorg Med Chem. 2024 Feb 16;101:117645. doi: 10.1016/j.bmc.2024.117645. Online ahead of print.ABSTRACTAll three possible sulfamate derivatives of the selective estrogen receptor modulator Raloxifene (bis-sulfamate 7 and two mono-sulfamates 8-9) were synthesized and evaluated as inhibitors of the clinical drug target steroid sulfatase (STS), both in cell-free and in cell-based assays, and also as estrogen receptor (ER) modulators. Bis-sulfamate 7 was the most potent STS inhibitor with an IC50 of 12.2 nM in a whole JEG3 cell-based assay, with the two mono-sulfamates significantly weaker. The estrogen receptor-modulating act...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Seyed-Omar Zaraei Wolfgang Dohle Hanan S Anbar Randa El-Gamal Bertrand Leblond Paul A Foster Taleb H Al-Tel Barry V L Potter Mohammed I El-Gamal Source Type: research

Research progress of LSD1-based dual-target agents for cancer therapy
Bioorg Med Chem. 2024 Feb 21;101:117651. doi: 10.1016/j.bmc.2024.117651. Online ahead of print.ABSTRACTLysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Xiaojuan Yang Source Type: research

Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
Bioorg Med Chem. 2024 Feb 18;101:117649. doi: 10.1016/j.bmc.2024.117649. Online ahead of print.ABSTRACTSimple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from ...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Ivana I Jevti ć Relja V Suru čić Gordana Tovilovi ć-Kovačević Nevena Zogovi ć Sla đana V Kostić-Rajačić Deana B Andri ć Jelena Z Penji šević Source Type: research

Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents
Bioorg Med Chem. 2024 Feb 16;101:117645. doi: 10.1016/j.bmc.2024.117645. Online ahead of print.ABSTRACTAll three possible sulfamate derivatives of the selective estrogen receptor modulator Raloxifene (bis-sulfamate 7 and two mono-sulfamates 8-9) were synthesized and evaluated as inhibitors of the clinical drug target steroid sulfatase (STS), both in cell-free and in cell-based assays, and also as estrogen receptor (ER) modulators. Bis-sulfamate 7 was the most potent STS inhibitor with an IC50 of 12.2 nM in a whole JEG3 cell-based assay, with the two mono-sulfamates significantly weaker. The estrogen receptor-modulating act...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Seyed-Omar Zaraei Wolfgang Dohle Hanan S Anbar Randa El-Gamal Bertrand Leblond Paul A Foster Taleb H Al-Tel Barry V L Potter Mohammed I El-Gamal Source Type: research

Research progress of LSD1-based dual-target agents for cancer therapy
Bioorg Med Chem. 2024 Feb 21;101:117651. doi: 10.1016/j.bmc.2024.117651. Online ahead of print.ABSTRACTLysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Xiaojuan Yang Source Type: research

Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
Bioorg Med Chem. 2024 Feb 18;101:117649. doi: 10.1016/j.bmc.2024.117649. Online ahead of print.ABSTRACTSimple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from ...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Ivana I Jevti ć Relja V Suru čić Gordana Tovilovi ć-Kovačević Nevena Zogovi ć Sla đana V Kostić-Rajačić Deana B Andri ć Jelena Z Penji šević Source Type: research

Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents
Bioorg Med Chem. 2024 Feb 16;101:117645. doi: 10.1016/j.bmc.2024.117645. Online ahead of print.ABSTRACTAll three possible sulfamate derivatives of the selective estrogen receptor modulator Raloxifene (bis-sulfamate 7 and two mono-sulfamates 8-9) were synthesized and evaluated as inhibitors of the clinical drug target steroid sulfatase (STS), both in cell-free and in cell-based assays, and also as estrogen receptor (ER) modulators. Bis-sulfamate 7 was the most potent STS inhibitor with an IC50 of 12.2 nM in a whole JEG3 cell-based assay, with the two mono-sulfamates significantly weaker. The estrogen receptor-modulating act...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Seyed-Omar Zaraei Wolfgang Dohle Hanan S Anbar Randa El-Gamal Bertrand Leblond Paul A Foster Taleb H Al-Tel Barry V L Potter Mohammed I El-Gamal Source Type: research

Research progress of LSD1-based dual-target agents for cancer therapy
Bioorg Med Chem. 2024 Feb 21;101:117651. doi: 10.1016/j.bmc.2024.117651. Online ahead of print.ABSTRACTLysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Xiaojuan Yang Source Type: research

Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
Bioorg Med Chem. 2024 Feb 18;101:117649. doi: 10.1016/j.bmc.2024.117649. Online ahead of print.ABSTRACTSimple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from ...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Ivana I Jevti ć Relja V Suru čić Gordana Tovilovi ć-Kovačević Nevena Zogovi ć Sla đana V Kostić-Rajačić Deana B Andri ć Jelena Z Penji šević Source Type: research

Synthesis, biological evaluation, and stability studies of raloxifene mono- and bis-sulfamates as dual-targeting agents
Bioorg Med Chem. 2024 Feb 16;101:117645. doi: 10.1016/j.bmc.2024.117645. Online ahead of print.ABSTRACTAll three possible sulfamate derivatives of the selective estrogen receptor modulator Raloxifene (bis-sulfamate 7 and two mono-sulfamates 8-9) were synthesized and evaluated as inhibitors of the clinical drug target steroid sulfatase (STS), both in cell-free and in cell-based assays, and also as estrogen receptor (ER) modulators. Bis-sulfamate 7 was the most potent STS inhibitor with an IC50 of 12.2 nM in a whole JEG3 cell-based assay, with the two mono-sulfamates significantly weaker. The estrogen receptor-modulating act...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Seyed-Omar Zaraei Wolfgang Dohle Hanan S Anbar Randa El-Gamal Bertrand Leblond Paul A Foster Taleb H Al-Tel Barry V L Potter Mohammed I El-Gamal Source Type: research

Research progress of LSD1-based dual-target agents for cancer therapy
Bioorg Med Chem. 2024 Feb 21;101:117651. doi: 10.1016/j.bmc.2024.117651. Online ahead of print.ABSTRACTLysine-specific demethylase 1 (LSD1) is a histone lysine demethylase that is significantly overexpressed or dysregulated in different cancers and plays important roles in cell growth, invasion, migration, immune escape, angiogenesis, gene regulation, and transcription. Therefore, it is a superb target for the discovery of novel antitumor agents. However, because of their innate and acquired resistance and low selectivity, LSD1 inhibitors are associated with limited therapeutic efficacy and high toxicity. Furthermore, LSD1...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Xiaojuan Yang Source Type: research

Multi-target potential of newly designed tacrine-derived cholinesterase inhibitors: Synthesis, computational and pharmacological study
Bioorg Med Chem. 2024 Feb 18;101:117649. doi: 10.1016/j.bmc.2024.117649. Online ahead of print.ABSTRACTSimple and scalable synthetic approach was used for the preparation of thirteen novel tacrine derivatives consisting of tacrine and N-aryl-piperidine-4-carboxamide moiety connected by a five-methylene group linker. An anti-Alzheimer disease (AD) potential of newly designed tacrine derivatives was evaluated against two important AD targets, acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE). In vitro pharmacological evaluation showed strong ChE inhibitory activity of all compounds, with IC50 values ranging from ...
Source: Bioorganic and Medicinal Chemistry - February 24, 2024 Category: Chemistry Authors: Ivana I Jevti ć Relja V Suru čić Gordana Tovilovi ć-Kovačević Nevena Zogovi ć Sla đana V Kostić-Rajačić Deana B Andri ć Jelena Z Penji šević Source Type: research

Identification of benzothiazole derived monosaccharides as potent, selective, and orally bioavailable inhibitors of human and mouse galectin-3; a rare example of using a S ···O binding interaction for drug design
Bioorg Med Chem. 2024 Feb 11;101:117638. doi: 10.1016/j.bmc.2024.117638. Online ahead of print.ABSTRACTAs a result of our continued efforts to pursue Gal-3 inhibitors that could be used to fully evaluate the potential of Gal-3 as a therapeutic target, two novel series of benzothiazole derived monosaccharides as potent (against both human and mouse Gal-3) and orally bioavailable Gal-3 inhibitors, represented by 4 and 5, respectively, were identified. These discoveries were made based on proposals that the benzothiazole sulfur atom could interact with the carbonyl oxygen of G182/G196 in h/mGal-3, and that the anomeric triazo...
Source: Bioorganic and Medicinal Chemistry - February 23, 2024 Category: Chemistry Authors: Chunjian Liu Wei Wang Jianxin Feng Brett Beno Thiruvenkadam Raja Jacob Swidorski Raju K V L P Manepalli Muthalagu Vetrichelvan Prasada Rao Jalagam Satheesh K Nair Anuradha Gupta Manoranjan Panda Kaushik Ghosh Jinal Kaushikkumar Shukla Harinath Sale Devang Source Type: research