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

Abstract

Current research is based on the identification of novel inhibitors of α-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, 1H-NMR and 13C-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 α-amylase inhibitory, DPPH and ABTS radical scavenging activities. All compounds showed good inhibition potential in the range of IC50v = 2.186-3.405 μM as compared to standard acarbose having IC50v value of 1.9 ± 0.07 μM. It is worth mentioning that compounds were also demonstrated good DPPH (IC50v = 0.09-2.233 μM) and ABTS (IC50v = 0.584-3.738 μM) radical scavenging activities as compared to standard ascorbic acid having IC50v = 0.33 ± 0.18 μM for DPPH and IC50v = 0.53 ± 0.3 μM 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 α-amylase enzyme.