In-silico study of the bioactive compounds of Blighia sapida koenig revealed a novel Plasmodium falciparum Dihydroorotate dehydrogenase inhibitor for malaria

Facing drug-resistant malaria, this study evaluated the antimalarial potential of bioactive compounds from B. sapida ethanolic leaf extract using in silico approachGas chromatography-mass spectroscopy (GC-MS) analysis was carried out to identify the compounds present in the extract. Molecular docking and dynamic simulation were done to evaluate interactions and stability between the lead compounds and the target protein, PfDHODH using Autodock vinna and Gromacs software respectively.Twenty-one compounds were identified from GC-MS analysis of the extract. The three predominant identified phytochemicals were D-Fructose 3-O-methyl- (21.02%), Phytol (20.77%) and Hexadecanoic acid, ethyl ester (13.11%). Complementary in silico molecular docking studies revealed interactions between the 21 compounds and PfDHODH. Seven compounds exhibited pronounced binding affinities (-17.4Kcal/mol to -7.4 Kcal/mol) when compared to the positive control, chloroquine (-7.2 Kcal/mol). Phytol, Ethyl 9,12,15-octadecatrienoate, Hexadecanoic acid methyl ester, Linoleic acid ethyl ester, and Hexadecanoic acid, ethyl ester demonstrated commendable drug-like characteristics and also showed good ADMET properties. Phytol was identified as the most stable inhibitor (RMSD- 0.176, ROG- 1.92, SASA- 166.9, Hydrogen bond- 2.02), followed by Ethyl 9,12,15-octadecatrienoate (RMSD- 0.191, ROG- 1.92, SASA- 171.1, Hydrogen bond- 0.57).These findings emphasize the potential antimalarial properties of B. sapida and shed light on its bioactive compounds.