Design of some Apigenin derivatives as selective DPP-IV Inhibitors by Pharmacophore Modelling and its Validation through Molecular Dynamics Simulation

Abstract

One of the most common forms of diabetes, type-2 diabetes mellitus is a chronic metabolic condition brought on by problems with insulin production or insulin resistance. By modifying blood glucose homeostasis, dipeptidyl peptidase-IV (DPP-IV) inhibition has the potential to treat type 2 diabetes. The quick development of computational drug design provided a fantastic opportunity to both discover and forecast the effectiveness of potential DPP-IV inhibitors. The current investigation supports and verifies the identification of new Apigenin derivatives as selective DPP-IV inhibitors. Schrodinger software was used to perform virtual screening (VS) of created compounds against DPP-IV, and the most promising hits were chosen. Out of 110 substances, 56 new apigenin derivatives were chosen for additional docking investigations using Glide based on their selectivity threshold followed by validation by pose selection method which is found to be below 2 Ǻ based on their superimposion with co-crystallized lgand. The DPP-IV protein was used as the target of molecular dynamic (MD) simulation studies to evaluate the correct binding mechanisms and stability of their complexes with enzyme. Structural chemistry was utilised to guide and considerably speed up the drug discovery process during the back-up development stages. It was also used to analyse in-silico suggestions and screening results, as well as to come up with fresh ideas. The study thus demonstrates the possibility of apigenin derivatives as highly specific DPP-IV inhibitors.