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

Novel carbazole-thiadiazole derivatives as α-amylase and α-glucosidase inhibitors: Design, biological evaluation, and computational insights DOI
İrfan Çapan, Mohammed Hawash, Mohammed T. Qaoud

et al.

Bioorganic Chemistry, Journal Year: 2025, Volume and Issue: unknown, P. 108243 - 108243

Published: Feb. 1, 2025

Language: Английский

Citations

0
Design, synthesis and in vitro biological evaluation of new coumarin containing oxazole hybrid derivatives as multitarget inhibitor of α-amylase and α-glucosidase for the treatment of diabetes DOI Creative Commons
Rafaqat Hussain,

Muhammad Nabi,

Shoaib Khan

et al.

Results in Chemistry, Journal Year: 2024, Volume and Issue: 9, P. 101638 - 101638

Published: July 1, 2024

Sixteen new coumarin-based oxazole derivatives were synthesized and their structures characterized by employing various spectroscopic tools including HREI-MS NMR. The in vitro assessment of α-amylase α-glucosidase inhibitory activities revealed that compound 1 (bearing trifluoro methyl at 4-position aryl ring D) & 16 (having 3-hydroxy 4-fluoro groups on exhibited potent potentials with IC50 values 0.70 ± 0.05 0.90 (against α-amylase) 1.10 0.10 1.20 α-glucosidase) respectively. Analogs 2, 3, 4, 5, 10 14 also displayed better compared to known acarbose inhibitor. Furthermore, the molecular docking studies analogs docked within active site cavity both showed enhanced binding interaction good predicted affinities. These compounds could therefore be considered as lead molecules for development potentially improved inhibitors.

Language: Английский

Citations

4
A promising α-glucosidase and α-amylase inhibitors based on benzimidazole-oxadiazole hybrid analogues: Evidence based in vitro and in silico studies DOI Creative Commons
Hayat Ullah, Imad Uddin,

Hafeeza Zafar Ali

et al.

Results in Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 101832 - 101832

Published: Sept. 1, 2024

Language: Английский

Citations

2
Synthesis and biological evaluation of substituted benzohydrazide Schiff base adduct as potential cholinesterase inhibitors DOI

Zulfiqar Ahmad,

Irshad Ullah Khan,

Muhammad Nabi

et al.

Chemical Data Collections, Journal Year: 2024, Volume and Issue: 52, P. 101151 - 101151

Published: June 13, 2024

Language: Английский

Citations

1
Design, synthesis, biological evaluation and molecular docking study of thiadiazole-isatin hybrid analogues as potential anti-diabetic and anti-bacterial agents DOI Creative Commons
Ghada Mohamed Aleid,

Shahzad Ahmad Abbasi,

Hayat Ullah

et al.

Results in Chemistry, Journal Year: 2024, Volume and Issue: unknown, P. 101805 - 101805

Published: Sept. 1, 2024

Language: Английский

Citations

1
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

1