Exploration of a Novel Indole/Pyrazole Scaffold as a Promising Dual α-Glucosidase and α-Amylase Inhibitor: an In Vitro, In Vivo and In Silico Approach Toward Antidiabetic Drug Design

Abstract

Objective: We aimed to develop a novel heterocyclic compound incorporating both indole and pyrazole moieties to assess its antidiabetic properties, as most existing antidiabetic medications, such as acarbose, voglibose, and miglitol, lack these specific structural features. Methods: The newly synthesized sulfonamide-based indole and pyrazole derivatives were characterized using mass spectrometry, ¹H, ¹³C NMR, IR, and techniques. In vitro and in vivo studies were conducted using Drosophila melanogaster as a model organism to evaluate toxicity and antidiabetic activity. Molecular modeling studies were performed using Sybyl-X, version 2.0. Results and Discussion: The results indicate that compound (C-04) (IC₅₀​ = 83.87 µM for α-amylase and IC₅₀​ = 73.15 µM for α-glucosidase) and compound (IVb) (IC₅₀​ = 63.34 µM for α-amylase and IC₅₀​ = 80.92 µM for α-glucosidase) exhibited significant enzyme inhibitory activities compared to acarbose, the positive control (IC₅₀​ = 35.17 µM). In addition, ADME properties of the synthesized compounds were analyzed using the SwissADME online tool. Further research can be conducted on compounds (IVb) and (C-04) to explore their potential as novel antidiabetic treatments by systematically increasing the dose, which may enhance their therapeutic efficacy. Conclusions: The findings suggest that compounds (C-04) and (IVb) hold promise for further development and could potentially undergo clinical trials in the future.