Synthesis and in Silico Docking Studies of Ethyl 2-(2-Arylidene-1-alkylhydrazinyl)thiazole-4-carboxylates as Antiglycating Agents

Abstract

Ethyl 2-(2-arylidene-1-alkylhydrazinyl)thiazole-4-carboxylates (1a–k) were synthesized by alkylation on HN- of ethyl 2-(2-arylidenehydrazinyl)thiazole-4-carboxylates. The proposed structures (1a–k) are corroborated by spectro-analytical techniques like UV, FT-IR, 1H-, 13C-NMR and HR-MS. All synthesized compounds were screened for their antiglycation and antioxidant assays. The in vitro antiglycation results revealed promising activity of compounds 1a, 1b, 1d, 1e, 1f, 1g, 1j and 1k with IC50 values 0.0004±1.097-17.22±0.538 μM when compared to standard, aminoguanidine (IC50=25.50±0.337 μM). Among all tested compounds 1j and 1k are the best antiglycating agents with IC50 values 1.848±0.646 and 0.0004±1.097 μM, respectively. The in-silico studies also agree with these results where binding energy for 1j and 1k was found to be −9.25 and −8.42 kcal/mol with calculated dissociation constants of 0.16 and 0.67 μM, respectively. The antiglycation results demonstrate the application of these compounds in reducing diabetic complications.