Computational assisted designing, screening, and synthesis of novel Inhibitor of malarial aspartic proteases Plasmepsin I

Abstract

Aspartic protease enzymes of Plasmodium falciparum such as plasmepsin I (PfPlm I) have been recognized as an interesting drug target for antimalarial drug discovery. For the immediate requirement of inhibitors of this enzyme, a computational approach was used to design HEA and piperazine analogs. We virtually screened 301 novel compounds based on validated pharmacophores i.e., hydroxyethyl amine (HEA) and piperazine against PfPlm I. The obtained hit compound in complex with PfPlm I was subjected for molecular dynamics (MD) simulations at 200ns and found stable. Hit compound was further validated by wet lab experiments.

 Keywords: Plasmepsin, Plasmodium, Proteases, Antimalarial drug, Analogs.