Work

Design, Synthesis, Antidiabetic Activity and In Silico Studies of New Hydrazone Derivatives Derived from Acetohexamide

Year: 2025

Type: article

Abstract: Diabetes is a well-known endocrine system disorder whose incidence has increased recently. The has been shown that the synthesis of new more effective antidiabetic drugs is needed because the drugs used in the treatment of diabetes have many side effects and are used in combination. Since hydrazone derivatives are very active compounds with antidiabetic effects, this aim of this study was to synthesize a series of hydrazone derivatives showing potential antidiabetic activity. In the inhibition activity of α-amylase and α-glucosidase, the compounds that showed the best inhibitory effect against both enzymes were determined as compounds 8 (IC50= 30.21±0.16 µM for α-amylase; IC50= 38.06±0.80 µM for α-glucosidase) and 10 (IC50= 34.49±0.37 µM for α-amylase; IC50= 40.44±0.23 µM for α-glucosidase). All of the compounds were evaluated for their cytotoxic effect by the 3-[4,5-dimethylthiazol-2-yl]-2,5-diphenyl tetrazolium bromide (MTT) test on the human embryonic kidney cell line (HEK293). Compounds 7 and 9 have been observed to kill half of the healthy HEK293 cells (IC50: 61.04 µM and IC50: 69.25 µM) respectively. Other compounds and the positive control acarbose showed no cytotoxic effects on healthy cells even at high concentrations. Additionally, the properties of molecules such as H-bond acceptors, H-bond donors, topological polar surface area (TPSA), Lipinski, iLogP, Gastrointestinal (GI) absorption, and Blood-Brain Barrier (BBB) permeability were also investigated with the SwissADME program used in drug design. Molecular docking simulations of the synthesized hydrazone derivatives, especially compounds 8 and 10, revealed strong interactions with α-glucosidase and α-amylase in their active sites.

Source: ACS Omega

DOI: 10.1021/acsomega.5c04642