Studies of Achyranthes aspera Shoot Phytochemicals on Plasmodium falciparum Dihydrofolate Reductase (PfDHFR) Enzymes Targeted in Antimalarial Drug Design

Resistance of Plasmodium falciparum to the first-line antimalarial drug (artemisinin) has been reported in several endemic regions, highlighting the need for new therapeutic alternatives. Medicinal plants are potential sources of bioactive compounds with antimalarial properties. Achyranthes aspera (Amaranthaceae) which is widely distributed in Africa and Nigeria, has shown significant antimalarial activity. This study investigated the in silico inhibitory effects of phytochemicals from the chloroform fraction of A. aspera against the Plasmodium falciparum dihydrofolate reductase (PfDHFR) enzyme. Bioactive compounds were identified and screened using molecular docking via AutoDock Vina 4.2 to evaluate their binding affinities to PfDHFR. Twelve phytochemicals demonstrated promising interactions with the target enzyme. Notably, Chikutsesusaponin iva (-9.4 kcal/mol) and Gypsogenin-3-O-glucuronide (-9.0 kcal/mol) exhibited stronger binding energies than standard inhibitors pyrimethamine (-5.6 kcal/mol) and cycloguanil (-5.8 kcal/mol). These lead compounds formed multiple traditional hydrogen bonds and other interactions within the PfDHFR binding pocket, suggesting a higher spontaneity and stability of binding. Some of the additional active compounds included are Betulin (-7.2 kcal/mol), Causapogenin (-7.8 kcal/mol), Gypsogenic acid (-7.9 kcal/mol), Kaempferol-3-O-galactoside (-6.9 kcal/mol), Lupeol (-7.8 kcal/mol), Lutein (-7.1 kcal/mol), Oleanolic acid (-7.6 kcal/mol), Squalene (-6.6 kcal/mol), and α-Spinasterol (-7.8 kcal/mol). These findings suggest that Chikutsesusaponin iva and Gypsogenin-3-O-glucuronide are promising candidates for antimalarial drug development targeting PfDHFR.