Due to the rising incidence of diabetes mellitus and the drawbacks of existing therapies, there is an urgent demand for new therapeutic agents targeting this condition. This research concentrates on developing novel compounds with potent alpha-glucosidase inhibitory activity, a key enzyme in managing diabetes. A series of 33 triazole derivatives was subjected to comprehensive QSAR analysis to determine the critical factors affecting their α-glucosidase inhibitory potency. Based on the multiple linear regression (MLR) model, seven potential drug candidates were designed. Molecular docking and dynamics simulations were performed to elucidate the interaction mechanisms between the ligands and the target enzyme, as well as the stability of the resulting complexes. In addition, the pharmacokinetic profiles of these designed compounds were evaluated to forecast their in vivo behavior. Binding free energies were computed using the MMGBSA method, indicating favorable thermodynamic characteristics. The findings identified three new compounds exhibiting high biological activity, strong binding affinity to the target enzyme, and good oral bioavailability. These outcomes provide promising opportunities for developing effective and well-tolerated antidiabetic drugs.
