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

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.