Synthesis of novel indole, 1,2,4-triazole derivatives as potential glucosidase inhibitors

Abstract

Objective: In the present study a series of eleven bis-heterocyclic compounds with indole derivative carrying 1,2,4-triazole moiety were synthesized and assessed for their in vitro α-amylase and α-glucosidase inhibition activity. Method: The synthesized compounds were characterized by using various spectroscopic techniques such as 1H NMR, IR and EI-MS. Initial in silico screening process was used to find potential ligands that were later evaluated for α-amylase and α-glucosidase inhibitory potential. Results: The docking results revealed that the synthesized compounds were well accommodated in the binding pockets of α-glucosidase. Especially, 5e and 5j showed similar interaction pattern, as previously reported Casuarine-enzyme complex. In vitro analysis suggests that compounds 5a-5k showed varying degrees of α-amylase and α-glucosidase inhibitory activity. Amongst them, 5e and 5j demonstrated good enzyme inhibition while remaining compounds showed low to moderate inhibitory potential. Conclusions: Addition of 2,5 dimethoxy substituent (2,5-dimethoxybenzaldehyde) (5e) or hydroxy, methoxy substituents (6-methoxy-2-naphthol aldehyde) (5j) at ortho and meta position exhibited good α-amylase and α-glucosidase inhibition. Hence this study provides several insights on improving the pharmacological profile of triazole containing compounds that can be adopted to design and develop novel glucosidase inhibitors.

Keywords

• α-Amylase
• α-Glucosidase
• Molecular docking
• Indole
• Triazole