In Silico Docking, ADMET and QSAR Study of few Antimalarial Phytoconstituents as Inhibitors of Plasmepsin II of P. falciparum Against Malaria

Abstract

Background: Malaria is endemic in various parts of India particularly in the North-Eastern states with Plasmodium falciparum the most prevalent human malaria parasite. Plant-derived compounds have always received tremendous importance in the area of drug discovery and development and scientific study of traditional medicinal plants are of great importance to mankind. Objective: The present work deals with the computational study of some antimalarial compounds obtained from few medicinal plants used by the tribal inhabitants of the North-Eastern region of India for treating malaria. Methods: In silico methodologies were performed to study the ligand-receptor interactions. Target was identified based on the pharmacophore mapping approach. A total of 18 plant-derived compounds were investigated in order to estimate the binding energies of the compounds with their drug target through molecular docking using Autodock 4.2. ADMET filtering for determining the pharmacokinetic properties of the compounds were done using Mobyle@RPBS server. Subsequent Quantitative-Structure Activity Relationship analysis for bioactivity prediction (IC50) of the compounds was done using Easy QSAR 1.0. Results: The docking result identified Salannin to be the most potent Plasmepsin II inhibitor while the QSAR analysis identified Lupeol to have the least IC50 value. Most of the compounds have passed the ADME/Tox filteration. Conclusion: Salannin and Lupeol were found to be the most potent antimalarial compounds that can act as successful inhibitors against Plasmepsin II of P. falciparum. The compounds Salannin and Lupeol are found in Azadirachta indica and Swertia chirata plants respectively, abundantly available in the North-Eastern region of India and used by many inhabiting tribes for treatment of malaria and its symptoms.

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“…Another crucial factor in determining oral bioavailability is molar refractivity (MR), defined by the Ghose rule 69 , and its value, as per the Lipinski rule 62 , should range from 40 to 130 for fulfilling the drug-likeness criteria by all compounds except A2, A6 , and C-6H . Besides, Ghose, Veber 70 , Egan 71 , and Muegge 72 rules were used to examine the drug-likeness of compounds. The compounds fulfill the rule of Veber and Muegge while the violation is shown by some compounds in the Egan rule (WLOGP > 500) by A2, A5, C6F , and C6G .…”