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-car-boxamide. 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 K 2 CO 3 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 1 H NMR, 13 C NMR, FTIR, and MS. Synthesized molecules were evaluated in vitro for their a-amylase inhibitory activity and displayed moderate to excellent inhibition with IC 50 values varying from 12.55 lg/mL to 69.47 lg/mL using acarbose (IC50 =23.62 lg/mL) as control. Moreover, a molecular docking study was carried out for synthesized molecules 4a-i against human pancreatic a-amylase (2QV4) via utilizing the Autodock technique. The docking outcomes of molecules 4g and 4h showed good cytotoxic activity.