New Hybrid Hydrazinyl Thiazole Substituted Chromones: As Potential α-Amylase Inhibitors and Radical (DPPH & ABTS) Scavengers

Current research is based on the identification of novel inhibitors of alpha-amylase enzyme. For that purpose, new hybrid molecules of hydrazinyl thiazole substituted chromones 5-27 were synthesized by multi-step reaction and fully characterized by various spectroscopic techniques such as EI-MS, HREI-MS, H-1-NMR and C-13-NMR. Stereochemistry of the iminic bond was confirmed by NOESY analysis of a representative molecule. All compounds 5-27 along with their intervening intermediates 1-4, were screened for in vitro alpha-amylase inhibitory, DPPH and ABTS radical scavenging activities. All compounds showed good inhibition potential in the range of IC50 = 2.186-3.405 mu M as compared to standard acarbose having IC50 value of 1.9 +/- 0.07 mu M. It is worth mentioning that compounds were also demonstrated good DPPH (IC50 = 0.09-2.233 mu M) and ABTS (IC50 = 0.584-3.738 mu M) radical scavenging activities as compared to standard ascorbic acid having IC50 = 0.33 +/- 0.18 mu M for DPPH and IC50 = 0.53 +/- 0.3 mu M for ABTS radical scavenging activities. In addition to that cytotoxicity of the compounds were checked on NIH-3T3 mouse fibroblast cell line and found to be non-toxic. In silico studies were performed to rationalize the binding mode of compounds (ligands) with the active site of alpha-amylase enzyme.