Exploring Triazole Derivatives as DPP IV Inhibitors: Advancing Type II Diabetes Treatment via Molecular Structure Investigation and Pharmacophore Modelling

Purpose Diabetes is a serious global health concern attributable to high rate of morbidity and mortality. Fortuitously, recent research has revealed the potential of glucagon-like peptide-1 (GLP-1) to regulate glucose homeostasis in type 2 diabetes patients. However, the dipeptidyl peptidase-IV (DPP-IV) enzyme degrades GLP-1, making it a target for anti-diabetic drug development. Methods In this scientific expedition, we set out on a quest to discover the novel potential DPP-IV inhibitors using cutting-edge pharmacophore modelling and molecular docking approaches. Our findings demonstrate a harmonious fusion of scientific advancement and therapeutic potential. Results The four-point pharmacophore model (AAHR_1) was developed using previously reported compounds, and a statistically significant 3D-QSAR model with an R 2 value of 0.94 and Q 2 value of 0.72 was generated using the best pharmacophore hypothesis. New triazole-linked phenylacetamide derivatives were predicted, synthesised and evaluated for their DPP IV inhibitory activity. Compound 8i showed interactions with S 1 (Tyr666), S 1 ’ (Tyr547), S 2 (Glu205), and S 2 ’ (Tyr547) subsites on the active site of the DPP-IV enzyme, making it a promising candidate for drug development. Conclusion Compounds 8d, 8f, 8 h, and 8i demonstrated significant invitro DPP-IV inhibitory activity in the range of 8.76 nM to 31.74 nM. These findings offer exciting possibilities for the development of new and effective treatments for type 2 diabetes.