Benzophenone Semicarbazones as Potential alpha-glucosidase and Prolyl Endopeptidase Inhibitor: In-vitro free radical scavenging, enzyme inhibition, mechanistic, and molecular docking studies

TL;DR

This study investigates benzophenone semicarbazones as potential inhibitors of alpha-glucosidase and prolyl endopeptidase, highlighting their antioxidant activity, enzyme inhibition, and molecular interactions for therapeutic development.

Contribution

It identifies specific benzophenone semicarbazone derivatives as dual inhibitors of alpha-glucosidase and prolyl endopeptidase with mechanistic and docking insights.

Findings

Seven derivatives showed free radical scavenging activity.

Fourteen derivatives inhibited alpha-glucosidase.

Nine derivatives inhibited prolyl endopeptidase.

Abstract

$\alpha$-glucosidase and prolylendopeptidase has altered expression and activity patterns in neurological disease, type 2diabetes respectively and several cancers. Here we screened a series 1-29 benzophenone semicarbazone derivatives for in vitro free radical scavenging, alpha-glucosidase and prolylendopeptidase inhibition activities. Seven derivatives were identified as potential free radical scavengers, 14 as alpha-glucosidase, and 9 as prolylendopeptidase inhibitors. Kinetic studies on the most promising inhibitors were performed. Compounds 23, 27, 25 and 28 were found as inhibitor of alpha-glucosidase, while compound 26 inhibited both prolylendopeptidase and alpha-glucosidase. The binding modes and binding free energy of the multi targeted inhibitor 26 were predicted by molecular docking studies. These results provide insights on prolylendopeptidase and alpha-glucosidase inhibition of compound 26 for further development as therapeutic agents for neoplastic, neurological, and endocrine disorders.