IN SILICO INVESTIGATIONS OF THE ANTIMALARIAL POTENTIAL OF PHYTOCONSTITUENTS OF MONODORA MYRISTICA AND PARINARI EXCELSA

Abstract

Plasmepsin II has been identified as a therapeutic target in the Plasmodium falciparum’s life cycle and may lead to a drastic reduction in deaths caused by malaria worldwide. African plants are rich in bioactive phytochemicals in simple and complex forms. This study encompasses computational approaches like molecular docking, molecular dynamics simulation, and ADMET to evaluate the Plasmepsin II inhibitory properties of the phytochemicals isolated from African plants. Molecular docking was carried out to estimate the binding affinity of the phytochemicals extracted from plant species Monodora myristica and Parinari excelsa. Further, the result showed that the screened phytochemicals were stable in the enzyme’s binding pocket, whereas the extracts from P. excelsa showed higher binding affinities. The positive control standard used in this experiment is Artesunate, and it had a binding score of -7.6 kcal/mol, while the cocrystalized ligand had a binding score of -9.3. A compound with PubChem CID 543400 of M .myristica had a binding score of -7.1 kcal/mol, which could be compare with that of Artesunate (-7.6 kcal/mol). Others had lower binding scores. For P. excelsa, a compound with PubChem CID 534435 had a binding score of -9 kcal/mol which can be compared to the binding affinity of the co-crystalized ligand of Plasmepsin II with -9.3 kcal/mol. Three others with PubChem CID’s 222284, 5368333 & 562543 had binding scores of -8.3, -8.6 & -8.3 kcal/mol, respectively, while others were found to have affinities from -7.1 kcal/mol to -7.9 kcal/mol. ADMET studies established the drug candidacy of the phytochemicals. The druglikeness study of the compounds of M. myristica and P. excelsa show that none of the molecules from the two plants failed the Lipinski rule of five. Even though few compounds had one violation to this rule, they passed the test because a compound is said to fail the test if it has more than one violation (Lipinski et al., 2001). The toxicity study also show that compounds of M. myristica show few major organ toxicity as the compound with PubChem CID 543400 showed none; whereas, most compounds of P. excelsa show one or two major organ toxicity. Thus, these phytochemicals could be assessed extensively via in vivo studies thereby acting as lead compounds for antimalarial.