Design of new potential DPP-4 inhibitors derived from benzene using molecular modeling

Abstract

Diabetes is a chronic disease that has become widespread in recent decades. The enzyme dipeptidyl peptidase 4 (DPP-4) plays an important role in the pathogenesis of diabetes, as it degrades incretin hormones secreted from the small intestines, which are responsible for stimulating insulin secretion from pancreatic beta cells and promoting the proliferation of these cells. This has drawn attention to the ability of inhibiting this enzyme to reduce blood glucose levels after meals. Therefore, this study aimed to find effective inhibitors of the DPP-4 enzyme using molecular modeling studies. Inhibitors derived from the benzene scaffold were designed to meet the unique structural requirements of the active site. A molecular docking study was conducted for these compounds to evaluate their binding to the enzyme's active site. The docking study indicated a good binding between the active site and compound number 1, derived from benzene. The kinetic and toxicological properties of these compounds were also evaluated.