Identification of Potential Inhibitors of <i>Plasmodium falciparum</i> L‐lactate Dehydrogenase From Selected African Compound Libraries: Virtual Screening, Molecular Mechanics‐Generalized Born Surface Area, and Molecular Dynamics Studies

Abstract

We evaluated 4,512 natural products from natural product library from Central African medicinal plants for drug discovery and South African natural compounds database libraries for the identification of potential Plasmodium falciparum L-lactate dehydrogenase inhibitors considering the virtual screening process. Extra precision virtual screening enabled the ranking of the top hundred hit molecules based on their docking properties. The selected hits were further shortened based on docking and molecular mechanics-generalized born surface area parameters in comparison with the reference. As a result, four hits were chosen: Mol1, Mol2, Mol3, and Mol4, all of them from the chalcone and quinone families. These molecules showed good predicted absorption, distribution, metabolism, and excretion, and toxicity properties. Finally, the molecular dynamics simulation results showed that the three chalcones, Mol1-4, formed an H-bond, hydrophobic interaction with key amino acids in the active site. This in silico study suggests that the chalcone compounds could serve as a potential source for developing new effective antimalarial drugs to combat malaria. Further in vitro or in vivo studies might be conducted to determine their actual effectiveness.