Synthesis, In Vitro α-Glucosidase Inhibitory Activity and Molecular Docking Study of New Benzotriazole-Based Bis-Schiff Base Derivatives

Abstract

This study was carried out to synthesize benzotriazole-based bis-Schiff base scaffolds (1–20) and assess them in vitro for α-glucosidase inhibitory potentials. All the synthetics analogs based on benzotriazole-based bis-Schiff base scaffolds were found to display an outstanding inhibition profile on screening against the α-glucosidase enzyme. The synthetic scaffolds showed a varied range of inhibition profiles having IC50 values ranging from 1.10 ± 0.05 µM to 28.30 ± 0.60 µM when compared to acarbose as a standard drug (IC50 = 10.30 ± 0.20 µM). Among the series, fifteen scaffolds 1–3, 5, 6, 9–16, 18–20 were identified to be more potent than standard acarbose, while the five remaining scaffolds 4, 7, 8, 16, and 17, also showed potency against the α-glucosidase enzyme but were found to be less potent than standard acarbose. The structure of all the newly synthesized scaffolds was confirmed using different spectroscopic techniques such as HREI-MS and 1H- and 13C- NMR spectroscopy. To find a structure-activity relationship, molecular docking studies were carried out to understand the binding mode of the active inhibitors with the active sites of the enzyme and the results supported the experimental data.

Keywords

• synthesis
• α-glucosidase
• benzotriazole
• bis-Schiff base
• structure activity relationship
• molecular docking