Synthesis of Arylidenehydrazinyl‐4‐methoxyphenylthiazole Derivatives: Docking Studies, Probing Type II Diabetes Complication Management Agents

Mehmood, Hasnain; Akhtar, Tashfeen; Haroon, Muhammad; Tahir, Ehsaan; Ehsan, Muhammad; Woodward, Simon; Musa, Mustapha

Abstract

Thiazole has been a key scaffold in antidiabetic drugs. In quest of new and more effective drugs a simple, efficient, high yielding (67–79 %) and convenient synthesis of arylidenehydrazinyl-4-methoxyphenyl)thiazoles is accomplished over two steps. The synthesis involved the condensation of aryl substituted thiosemicarbazones and 2-bromo-4-methoxyacetophenone in absolute ethanol. The structures of the resulting thiazoles are in accord with their UV/VIS, FT-IR, 1H-, 13C-NMR and HRMS data. All compounds were evaluated for alpha(α)-amylase inhibition potential, antiglycation, antioxidant abilities and biocompatibility. The compounds library identified 2-(2-(3,4-dichlorobenzylidene)hydrazinyl)-4-(4-methoxyphenyl)thiazole as a lead molecule against α-amylase inhibition with an IC50 of 5.75±0.02 μM. α-Amylase inhibition is also supported by molecular docking studies against α-amylase. All the obtained thiazoles also showed promising antiglycation activity with 4-(4-methoxyphenyl)-2-{2-[2-(trifluoromethyl)benzylidene]hydrazinyl}thiazole exhibiting the best inhibition (IC50= 0.383±0.001 mg/mL) compared to control. The tested compounds are also biocompatible at the concentration used i. e., 10 μM.

• Journal Article Type: Article
• Acceptance Date: Oct 3, 2022
• Online Publication Date: Oct 26, 2022
• Publication Date: 2022-11
• Deposit Date: Nov 30, 2022
• Publicly Available Date: Oct 27, 2023
• Journal: Chemistry and Biodiversity
• Print ISSN: 1612-1872
• Electronic ISSN: 1612-1880
• Peer Reviewed: Peer Reviewed
• Volume: 19
• Issue: 11
• Article Number: e202200824
• DOI: https://doi.org/10.1002/cbdv.202200824
• Keywords: Molecular Biology, Molecular Medicine, General Chemistry, Biochemistry, General Medicine, Bioengineering
• Public URL: https://nottingham-repository.worktribe.com/output/12597528
• Publisher URL: https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202200824
• Additional Information: This is the peer reviewed version of the following article: H. Mehmood, T. Akhtar, M. Haroon, E. Tahir, M. Ehsan, S. Woodward, M. Musa, Chem. Biodiversity 2022, 19, e202200824, which has been published in final form at https://onlinelibrary.wiley.com/doi/10.1002/cbdv.202200824