Discovery of a selective, safe and novel anti-malarial compound with activity against chloroquine resistant strain of Plasmodium falciparum

Abstract

In recent years the DNA minor groove has attracted much attention for the development of antimalarial agents. In view of this we have attempted to discover novel DNA minor groove binders through in-silico and in-vitro workflow. A rigorously validated pharmacophore model comprising of two positive ionizable (PI), one hydrophobic (HY) and one ring aromatic (RA) features was used to mine NCI chemical compound database. This led to retrieval of many hits which were screened on the basis of estimated activity, fit value and Lipinski's violation. Finally two compounds NSC 639017 and NSC 371488 were evaluated for their in-vitro anti-malarial activities against Plasmodium falciparum 3D7 (CQ sensitive) and K1 (CQ resistant) strains by SYBR green-I based fluorescence assay. The results revealed that out of two, NSC 639017 posses excellent anti-malarial activity particularly against chloroquine resistant strain and moreover NSC 639017 also appeared to be safe (CC 50 126.04 μg/ml) and selective during cytotoxicity evaluation.