Next-Generation Carbazole-Linked 1,2,4-Triazole-Thione Derivatives: Strategic Design, Synthesis, Molecular Docking, and Evaluation of Antidiabetic Potential DOI Creative Commons
İrfan Çapan, Mohammed Hawash, Mohammed T. Qaoud

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 10(1), P. 848 - 861

Published: Dec. 25, 2024

Currently, available therapies for diabetes cannot achieve normal sugar values in a high percentage of treated patients. This work synthesized series carbazole-triazole-thione derivatives, and their potential antidiabetic activity was investigated against the key diabetic enzymes α-amylase glycosidase. Normal human hepatic stellate cells (LX-2) were employed to assess cytotoxicity safety, followed by vivo testing investigate hypoglycemic effect most promising agent. As result, set 18 carbazole-1,2,4-triazole-thione derivatives synthesized. Seven structures demonstrated inhibitory enzyme, with IC50 lower than 6.4 μM. Among them, compounds C5f, C5o, C5r exhibited highest potency, 0.56, 0.53, 0.97 μM, respectively, compared well-known inhibitor acarbose, which has an value 5.31 Exploring inhibition potency these α-glucosidase enzyme revealed that C5f act as moderate inhibitors, 11.03 13.76 respectively. Moreover, at 100 μM concentration, evaluated showed negligible cytotoxic LX-2 cell lines, particularly C5o C5s, 3-fold positive control 5-Flururicle (cell viability 13.45%). Thus, compound selected evaluation, after administering five doses this (10 mg/kg) group III mice, significant reduction glucose concentration observed, bringing it down from 290.54 216.15 mg/dL, comparison did not show blood level. These observed vitro results upheld performing chemoinformatic studies elucidated binding interactions active within enzyme's site highlighted critical roles both 1,2,4-triazole-3-thione carbazole scaffolds interactions. Finally, drug-likeness profiles our suggest candidates further clinical trials.

Language: Английский

Phytochemical-Mediated Green Synthesis of Silver, Copper, and Ag–Cu Bimetallic Nanoparticles Using Peganum harmala Demonstrating Advanced Catalytic, Antioxidant, and Biomedical Applications DOI
Amjid Khan, Muhammad Anas,

Fouzia Bibi

et al.

Applied Biochemistry and Biotechnology, Journal Year: 2025, Volume and Issue: unknown

Published: Feb. 18, 2025

Language: Английский

Citations

0
Next-Generation Carbazole-Linked 1,2,4-Triazole-Thione Derivatives: Strategic Design, Synthesis, Molecular Docking, and Evaluation of Antidiabetic Potential DOI Creative Commons
İrfan Çapan, Mohammed Hawash, Mohammed T. Qaoud

et al.

ACS Omega, Journal Year: 2024, Volume and Issue: 10(1), P. 848 - 861

Published: Dec. 25, 2024

Currently, available therapies for diabetes cannot achieve normal sugar values in a high percentage of treated patients. This work synthesized series carbazole-triazole-thione derivatives, and their potential antidiabetic activity was investigated against the key diabetic enzymes α-amylase glycosidase. Normal human hepatic stellate cells (LX-2) were employed to assess cytotoxicity safety, followed by vivo testing investigate hypoglycemic effect most promising agent. As result, set 18 carbazole-1,2,4-triazole-thione derivatives synthesized. Seven structures demonstrated inhibitory enzyme, with IC50 lower than 6.4 μM. Among them, compounds C5f, C5o, C5r exhibited highest potency, 0.56, 0.53, 0.97 μM, respectively, compared well-known inhibitor acarbose, which has an value 5.31 Exploring inhibition potency these α-glucosidase enzyme revealed that C5f act as moderate inhibitors, 11.03 13.76 respectively. Moreover, at 100 μM concentration, evaluated showed negligible cytotoxic LX-2 cell lines, particularly C5o C5s, 3-fold positive control 5-Flururicle (cell viability 13.45%). Thus, compound selected evaluation, after administering five doses this (10 mg/kg) group III mice, significant reduction glucose concentration observed, bringing it down from 290.54 216.15 mg/dL, comparison did not show blood level. These observed vitro results upheld performing chemoinformatic studies elucidated binding interactions active within enzyme's site highlighted critical roles both 1,2,4-triazole-3-thione carbazole scaffolds interactions. Finally, drug-likeness profiles our suggest candidates further clinical trials.

Language: Английский

Citations

2