Computational analysis of luteolin, apigenin and their derivatives from Allophylus africanus as potential inhibitors of plasmepsin II a malaria target.

Malaria remains a critical global health challenge, especially in Sub-Saharan Africa, with drug-resistant strains heightening the need for new treatment strategies. Plasmepsin II, a key enzyme in the life cycle of malaria presents a promising target for novel antimalarial drugs. This study investigates the interaction of luteolin, apigenin and their glycoside derivatives from Allophylus africanus with PMII target using molecular docking, molecular dynamics simulation and free energy calculations. Luteolin derivatives, particularly luteolin-7-O-glucoside and luteolin-3',7-di-O-glucoside showed strong binding with PMII at -9.1 and -9.5 kcal/mol, respectively, while in apigenin derivatives apigenin-6,8-di-C-hexoside exhibited the most significant binding energy (-10.2 kcal/mol). The free energy calculations further confirmed the strong binding affinity with the apigenin-8-C-hexoside, demonstrating the best binding free energy (-86.646 kJ/mol). The study highlights the potential of these compounds as promising candidates for antimalarial drug development, although further experimental validation is needed.