In Silico Molecular Docking and Pharmacokinetics Studies on Potential Plasmodium falciparum Casein Kinase-2 Alpha (PfCK-2α) Inhibitors from Alstonia boonei Stem Bark

Although significant efforts have been made to reduce the malaria burden, the development and spread of resistance by the malaria parasite have necessitated the development of better alternatives to existing therapies. The role of Plasmodium falciparum casein kinase-2 alpha (PfCK-2α) in sexual and asexual blood stages highlights its potential as a target for multistage antimalarial drugs. This study aimed to determine the antimalarial potential of bioactive compounds from Alstonia boonei stem bark using computational methods. The bioactive constituents were characterized using UPLC-QTOF-MS, and the identified compounds were docked against Plasmodium falciparum casein kinase-2 alpha (PfCK-2α) using Molecular docking tools. UPLC-QTOF-MS analysis structurally characterized 85 compounds. Ricinoleic acid and corosolic acid are among the compounds showing high retention times. Docking studies revealed that the selected compounds demonstrated higher binding affinity (-8.6 to -11.0 kcal/mol) than the standard drug (Artesunate) (-7.8 kcal/mol). These compounds interacted favorably with the binding pocket amino acid residues (Lys72, Ile120, Ser179, Tyr119, Tyr54, Glu118, and Ser55). This study, therefore, demonstrates the antimalarial potential of the A. boonei phytoconstituents against PfCK-2α. Although this study holds a lot of promise, further investigation of the safety and efficiency of these identified compounds is required.