Novel inhibitors designing against the potential drug target of Plasmodium falciparum M17 Leucyl Aminopeptidase - PfM17LAP

Abstract

Malaria is one of the major disease of concern worldwide especially in the African regions. According to the recent WHO reports, African regions share 95% of the total deaths worldwide that occurs due to malaria. Plasmodium falciparum M17 Leucyl Aminopeptidase (PfM17LAP) plays an important role in the regulation of amino acids release and for the survival of the parasite. We performed molecular docking and simulation studies to find the potential inhibitors against PfM17LAP using ChEMBL antimalarial library. Molecular docking studies and post-docking analysis revealed that molecules CHEMBL369831 and CHEMBL176888 showed better binding than the reference molecule BESTATIN. LibDock and X-SCORES of molecules BES, CHEMBL369831 and CHEMBL176888 are 130.071, 230.38, 223.56 and -8.75 Kcal/mol, -10.90 Kcal/mol, -11.05 Kcal/mol respectively. ADMET profiling of the top ten ranked molecules was done by using the Discovery Studio. Molecular dynamic studies revealed that the complex PfM17LAP-CHEMBL369831 is stable throughout the simulation. Finally, we have reported novel inhibitors which possess more binding affinity towards PfM17LAP.