Antimalarial Phytochemicals Identification from Euphorbia Hirta against Plasmepsin Protease: an In Silico Approach.

Abstract

Aspartic protease found in plasmodium parasites such as plasmepsin I, II and IV plays an important role in the degradation of hemoglobin. The studies have shown that effective drug must be able to inhibit more than one type of plasmepsin to avoid further growth of parasites and to prevent resistance of drug. Therefore, plasmepsins are believed to be excellent drug target for malarial disease. Extract of the plant Euphorbia hirta has been proved to exert antimalarial activity. However, molecular mechanism of this activity was not described. The aim of present investigation is to identify antimalarial phytochemicals of Euphorbia hirta as plasmepsin protease inhibitors using an in silico approach. Docking studies were performed on three different protein targets plasmepsin I, II, and IV using iGEMDOCK. ADME and bioactivity predictions were done using molinspiration online tool. Toxicity studies were performed using ProTox-II online tool. In the docking studies seven compounds showed significant inhibitory activity with low docking score as compared to standard drug artemisinin. Six compounds showed no violations as per Lipinski rule. Bioactivity prediction states that all the compounds may act through enzyme inhibition. The results of in silico studies suggest that out of the eleven selected phytochemicals isorhamnetin and pinocembrin have more drug likeliness properties and lesser in silico toxicity with more binding affinity than artemisinin on all receptors. These findings indicate that isorhamnetin and pinocembrin have promising potential for development of antimalarial drug as plasmepsin inhibitors.