Anti-diabetic agents from natural origin like dipeptidyl peptidase IV inhibitors: Phamacophore based virtual and docking studies

Abstract

Dipeptidyl peptidase IV is a serine protease that rapidly cleaves glucagon-likepeptide-1 and glucose-dependent insulinotropic polypeptide. Inhibition of Dipeptidyl peptidase IV would prolong the half-life of incretins which stimulates insulin secretion. Omarigliptin which is in phase 3 clinical trial has added benefits over currently available Dipeptidyl peptidase IV inhibitors in terms of Specificity towards Dipeptidyl peptidase IV and due to its pharmacokinetic profile. Hence, our present study aims at identifying potential Dipeptidyl peptidase IV inhibitors which are having similar structural features with that of omarigliptin. First, we have identified 3 D structural features of omarigliptin to build a pharmacophore model. The built pharmacophore model was used to screen 55 250 drug like molecules with diverse structures from natural origin. The 78 molecules with a good Qfit values were filtered for further docking study against Dipeptidyl peptidase IV receptor to validate the screening protocol. The docking scores were found to be in congruent with the virtual screening protocol. The candidate molecules which needs further attention was found to be the ZINC38549932, ZINC72325326, ZINC98363871, ZINC201111835 and ZINC39999688.The illustration regarding the virtual screening protocol followed for identifying the Dipeptidyl peptidase IV inhibitors is reported here.