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 IC(50) range of 14.69-38.71 nmol in comparison with the positive drug Acarbose (IC(50) 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 CF(3) 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.