Computational Screening of Djiboutian Medicinal Plants Reveals Potential Dual Inhibitors Against

objectivesMalaria remains a major global health burden, particularly in endemic regions such as Djibouti, where

methodsA library of 222 phytoconstituents was screened against

resultsSeveral phytoconstituents exhibited strong binding affinities, with docking scores ranging from -6.09 to -7.54 kcal/mol, outperforming the reference drug artemisinin. Interaction analysis revealed key hydrogen bonds and hydrophobic contacts with essential active-site residues. ADMET predictions indicated favorable pharmacokinetic profiles, including high oral absorption, good membrane permeability, and low predicted toxicity. Molecular dynamics simulations demonstrated stable behavior for most complexes, with compound 121 showing enhanced stability in the 1J3K system and compound 123 exhibiting consistent dynamic stability in the 3IHZ system. In contrast, compound 82 displayed greater structural fluctuations despite maintaining stable hydrogen bond interactions.

conclusionsThe integration of molecular docking, ADMET prediction, and molecular dynamics simulations identified compounds 121 and 123 as the most promising antimalarial candidates, exhibiting an optimal balance of binding affinity, favorable pharmacokinetic properties, and dynamic stability. These findings highlight the potential of Djiboutian medicinal plants as a valuable source of novel antimalarial agents and provide a strong computational foundation for future experimental validation.