Designing and Virtual Screening of Potential Inhibitors of PFHGPRT against Malaria

Plasmodium falciparum is dangerous malarial species and most burdensome form of human malaria, affecting 200–300 million individuals per year worldwide, also because of its high rate of resistance outbreaks; there is a constant need for the discovery of novel antimalarials and drug targets. The three-dimensional structures of PFHGPRT, HSHGPRT and TCHGPRT were used for comparative docking study, while two inhibitors 6-(2, 2Dichloroacetamido) chrysene and GMP-2', 3'-dialdehydewere used as lead for designing and discovery of potential inhibitor of PFHGPRT with the help of Chimera and Molegro Virtual Docker. ZINC Pharmer and FAF-Drugs3 were used for pharmacophore and ADMET studies respectively. Results of structural superimposition and structural difference indicated that selective inhibitor of PFHGPRT could be designed. HGPRT inhibitor 6-(2,2dichloroacetamido) chrysene had shown more affinity for PFHGPRT than HSHGPRT and total 87 compounds used for screening (obtained through Pharmacophore based searching) were then virtually screened against the target PFHGPRT and on the basis of Moldock scoring two compound ZINC00226974 and ZINC00268007 were finally selected. Further studies clearly indicated that ZINC00226974 has more strong binding and thus will offer better PFHGPRT inhibition. Thus further synthesis, preclinical/clinical studies of such PFHGPRT inhibitors could help in controlling malaria more effectively.