IN SILICO DOCKING STUDIES OF BIOACTIVE NATURAL PRODUCTS AS PUTATIVE Pf-DHFR ANTAGONISTS

Abstract

Malaria is one of the serious hurdles to public health with about one million deaths annually. Present chemotherapies are inadequate because of the genesis and emergence of new drug resistance strains. So there is a urgent need to recognize new inhibitors against known or novel targets. Herein we are presenting docking studies of bioactive natural plant products against Pf DHFR. For this purpose we have built a library of 205 active molecules of plant origin having some folklore history as being used as antimalarial. Three docking engines AutoDock 4.2, MVD 5.0 (Molegro Virtual Docker) and iGEMDOCK 2.1 were used for Screening. AutoDock and iGEMDOCK runs resulted in the energy scores from -4.6 to -12.07 Kcal/mol and -63 to =156.2 kcal/mol respectively. Our analysis shows Ochrolifuanine and Chrobisiamine as most promising hit with K; in nanomolar range. We also focused on the common structure features of ligand and the residues of protein which remain almost conserved throughout the analysis. We hoped this work would aid in antimalarial combat strategies and can serve to provide new therapeuticals in a rapid manner