Synthesis, type II diabetes inhibitory activity and docking studies of novel thiazole molecules

Abstract

A series of novel ethyl (E)-2-cyano-3-((4-methyl-5-(arylcarbamoyl)thiazol-2-yl)amino)-3-(methylthio)acrylate have been synthesized starting from various 2-amino-N-aryl-4-methylthiazole-5-carboxamide. The reaction of 3-oxo-N-arylbutanamide 2a-i with N-bromosuccinimide and cyclization with thiourea under reflux conditions yielded derivatives of 2-amino-N-aryl-4-methylthiazole-5-carboxamide 3a-i. Further reaction of thiazoles 3a-i with ethyl 2-cyano-3,3-bis(methylthio)acrylate in DMF and K₂CO₃ as a base under room temperature gave new thiazole molecule 4a-i with excellent yields. The significant features of this reaction procedure are novel, modest, and short time. The spectral characterization of molecules was confirmed by ¹H NMR, ¹³C NMR, FTIR, and MS. Synthesized molecules were evaluated in vitro for their α-amylase inhibitory activity and displayed moderate to excellent inhibition with IC₅₀ values varying from 12.55 μg/mL to 69.47 μg/mL using acarbose (IC₅₀=23.62 μg/mL) as control. Moreover, a molecular docking study was carried out for synthesized molecules 4a-i against human pancreatic α-amylase (2QV4) via utilizing the Autodock technique. The docking outcomes of molecules 4g and 4h showed good cytotoxic activity.

Graphical abstract

An efficient procedure for synthesizing highly functionalized thiazole molecules, type II diabetes inhibitory activity with molecular docking studies.