Jamia Hamdard, India
Title: Identification of novel small molecule non-peptidomimetic inhibitor for Prolyl Oligopeptidase enzyme
Biography: Apeksha Shrivastava
The research on peptidomimetic inhibitors of Prolyl Oligopeptidase for various disorders viz. Alzheimer’s, Schizophrenia, Inflammation, Parkinson’s, Depression, etc. is being carried out since more than three decades, but still no drug have made it through the clinical trials, possibly because of poor pharmacokinetics. This might have engrained from the fact that all the structures submitted to the clinical trials were having similar chemical structures. Our study aimed at identifying novel small molecule non peptidomimetic inhibitor for prolyl oligopeptidase enzyme that could serve as starting point for developing newer drugs for inhibition of the enzyme. A structure based virtual screening of MDPI database was conducted on of prolyl Oligopeptidase enzyme (3DDU PDB ID), the identified hits were subjected to computational ADME screening, thereafter, MM/GBSA studies were performed to check the stability of the ligand-receptor complex. Nine hits were then subjected to prolyl oligopeptidase inhibitory assay in triplicates, among which one compound MM4 displayed good inhibitory potential of 100 µM. Furthermore, MD simulations of MM4 and reference was carried out to study the overall stability of lead-receptor complex and also to identify important interactions that were not apparent from docking study. Hence, discovery of novel small molecule non peptidomimetic prolyl Oligopeptidase inhibitor was accomplished.