Synthesis, anti-diabetic profiling and molecular docking studies of 2-(2- arylidenehydrazinyl)thiazol-4(5H)-ones

Mehmood, Hasnain; Haroon, Muhammad; Akhtar, Tashfeen; Woodward, Simon; Haq, Saadia; Alshehri, Saad M

Abstract

Aims: To synthesize novel more potent anti-diabetic agents. Methodology: A simple cost effective Hantzsch's synthetic strategy was used to synthesize 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones. Results: Fifteen new 2-(2-arylidenehydrazinyl)thiazol-4(5H)-ones were established to check their anti-diabetic potential. From alpha(α)-amylase inhibition, anti-glycation, and anti-oxidant activities it is revealed that most of the compounds showed good anti-diabetic potential. All tested compounds were found to be more potent anti-diabetic agents via anti-glycation mode. The results of amylase inhibition revealed that compounds are less active against α-amylase and antioxidant assays. Conclusions: This study concludes that introduction of various electron withdrawing groups at the aryl ring and substitution of different functionalities around thiazolone nucleus could help to find out better anti-diabetic drug. Graphical Abstract Lay Abstract Diabetic is a most spreading chronicle disease effecting millions of peoples across the globe every year and this number increases day by day. To cure human population from this dilemma, we had synthesized, characterized and evaluated the anti-diabetic behaviour of our synthesized compounds. α-Amylase, in vitro anti-glycation and anti-oxidant assays were performed to find out good lead for diabetes mellitus. All tested compounds were found as an excellent anti-glycating agents with IC50 values far better than standard amino-guanidine (IC50= 3.582±0.002 µM). Compound 4m was most efficient glycation inhibitor (IC50= 1.095±0.002 µM). Cytotoxicity of all compounds was determined with in vitro haemolytic assay and found all compounds safe and bio-compatible to humans at all tested concentrations. The inhibition potential was also examined with theoretical docking studies to support our experimental results against Human Pancreatic Alpha-amylase (HPA) and Human Serum Albumin (HSA) proteins. All compounds showed excellent binding affinity with HSA active pockets and only compound 4h and 4k binding affinity was good with HPA.

Citation

Mehmood, H., Haroon, M., Akhtar, T., Woodward, S., Haq, S., & Alshehri, S. M. (2024). Synthesis, anti-diabetic profiling and molecular docking studies of 2-(2- arylidenehydrazinyl)thiazol-4(5H)-ones. Future Medicinal Chemistry,

• Journal Article Type: Article
• Acceptance Date: Apr 8, 2024
• Online Publication Date: May 10, 2024
• Publication Date: May 10, 2024
• Deposit Date: May 16, 2024
• Publicly Available Date: May 11, 2025
• Print ISSN: 1756-8919
• Electronic ISSN: 1756-8927
• Publisher: Future Science
• Peer Reviewed: Peer Reviewed
• Keywords: Thiazol-4(5H)-ones; Anti-diabetic; Molecular docking; Cytotoxicity; SAR; NMR; HRMS
• Public URL: https://nottingham-repository.worktribe.com/output/34865501
• Publisher URL: https://www.future-science.com/doi/10.1080/17568919.2024.2342700
• Additional Information: For full bibliographic citation, please refer to the version available at https://www.future-science.com/doi/full/10.1080/17568919.2024.2342700