Synthesis of Some Novel Chalcone and 3,5-Disubstituted Pyrazoline Derivatives: Evaluation of Their α-Amylase and α-Glucosidase Inhibitory Activities In Vitro and In Silico

Abstract

This study reports the synthesis of some novel chalcone (C1-C3) and 3,5-disubstituted pyrazoline derivatives (P1-P3), structurally based on aminophenyl and trifluoromethylphenyl groups. Their potential as antidiabetic agents was evaluated through in vitro inhibition of α-amylase and α-glucosidase enzymes and supported by molecular docking studies. Among all the compounds, P2 showed potent dual inhibition, with IC₅₀ values of 9.35 and 2.10 µM against α-amylase and α-glucosidase, respectively, comparable to or better than the standard inhibitor acarbose. Kinetic studies revealed that P2 acts via a non-competitive mechanism for both enzymes. Docking analysis was performed for all of the molecules. These findings suggest that especially P2 has significant potential as a lead compound for further antidiabetic drug development.

Keywords: chalcones; molecular modeling; pyrazolines; α‐amylase inhibition; α‐glucosidase inhibition.