Novel and efficient synthesis of 5-chloro-6-methoxy-3-(2-((1-(aryl)-1H-1,2,3-triazol-4-yl)methoxy)ethyl)benzo[d]isoxazole derivatives as new α-glucosidase inhibitors

TL;DR

Scientists created new compounds that effectively inhibit an enzyme linked to diabetes and also show antibacterial properties.

Contribution

A new class of benzo[d]isoxazole-triazole hybrids was synthesized and shown to be potent α-glucosidase inhibitors.

Findings

The compounds showed α-glucosidase inhibition with IC50 values as low as 14.69 nmol.

Electron-withdrawing substituents like Br and CF3 improved enzyme inhibition.

Some compounds also exhibited antibacterial activity against B. cereus.

Abstract

A new series of benzisoxazole derivatives (9a-o) were designed by using molecular hybridization approach and synthesized via click-chemistry. All the synthesized compounds were evaluated for their α-glucosidase enzyme inhibition and antibacterial activity. All tested compounds (9a-o) exhibited a promising α-glucosidase inhibitory activity with IC50 range of 14.69–38.71 nmol in comparison with the positive drug Acarbose (IC50 35.91 nmol). Additionally, these compounds have found to be active against B. cereus and E. coli. The in vitro inhibition results supported to in silico. Additionally, the compounds were subjected to computational drug-likeness/ADME testing, which revealed that this all the compounds had good ADME profiles in addition to exhibiting drug-like qualities. SAR indicates that analysis revealed that electron-withdrawing substituents such as Br and CF3 at specific positions significantly enhanced α-glucosidase inhibition, while unsubstituted and ortho-methoxy phenyl derivatives also showed potent activity, highlighting the benzo[d]isoxazole–triazole scaffold as a promising pharmacophore for developing novel anti-diabetic agents.

•Novel benzo[d]isoxazole-triazole hybrids were synthesized as α-glucosidase inhibitors.•All compounds were prepared via Cu(I)-catalyzed click chemistry in good yields.•Compounds 9a and 9j showed top docking scores of −9.2 and −9.4 kcal/mol, respectively.•All derivatives showed potent α-glucosidase inhibition with IC50 range of 14.69–38.71 nmol.•Compounds 9f, 9h, and 9l showed antibacterial activity against Bacillus
cereus.

Novel benzo[d]isoxazole-triazole hybrids were synthesized as α-glucosidase inhibitors.

All compounds were prepared via Cu(I)-catalyzed click chemistry in good yields.

Compounds 9a and 9j showed top docking scores of −9.2 and −9.4 kcal/mol, respectively.

All derivatives showed potent α-glucosidase inhibition with IC50 range of 14.69–38.71 nmol.

Compounds 9f, 9h, and 9l showed antibacterial activity against Bacillus
cereus.

Figures