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

A series of indole-based bisacylhydrazone derivatives 4a similar to 4v were synthesized and assessed for their alpha-glucosidase activities. The results presented that all synthesized analogues exhibited excellent to moderate inhibitory effects on alpha-glucosidase. Compound 4j showed the highest alpha-glucosidase inhibition (IC50: 1.01 +/- 0.26 mu M). Inhibition kinetics results showed analogues 4j were reversible and mixed-type inhibitors against alpha-glucosidase. The results of Circular dichroism (CD) spectroscopy showed that the binding of alpha-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 alpha-glucosidase polypeptide backbone. Molecular docking revealed that compound 4j was well nested into the active pocket of alpha-glucosidase tightly binding to the amino acid residues of active pocket. (C) 2022 Elsevier B.V. All rights reserved.

Automated summary

A series of derivatives were synthesized and evaluated for their inhibitory activities on α-glucosidase. Compound 4j exhibited the highest inhibitory activity. Spectroscopy and docking results revealed the binding mechanism and mode of action of compound 4j on α-glucosidase.