Design, synthesis and evaluation of indole-based bisacylhydrazone derivatives as α-glucosidase inhibitors

Abstract

A series of indole-based bisacylhydrazone derivatives 4a∼4v were synthesized and assessed for their α-glucosidase activities. The results presented that all synthesized analogues exhibited excellent to moderate inhibitory effects on α-glucosidase. Compound 4j showed the highest α-glucosidase inhibition (IC50: 1.01 ± 0.26 µM). Inhibition kinetics results showed analogues 4j were reversible and mixed-type inhibitors against α-glucosidase. The results of Circular dichroism (CD) spectroscopy showed that the binding of α-glucosidase to compound 4j resulted in partial unfolding and loosening of the protein and some secondary structural change. Three dimensional (3D) fluorescence spectrometry predicted the microenvironments change of tyrosine and tryptophan residue and the structure change of the α-glucosidase polypeptide backbone. Molecular docking revealed that compound 4j was well nested into the active pocket of α-glucosidase tightly binding to the amino acid residues of active pocket.