Sunday Ayodele Alonge^1,4 , Isaac Iseoluwa Ajayi², Olajumoke Kemi Ekundayo², Oluwaseun Dorcas Ayo-Dada³, Abayomi Samuel Ayesa², Olufemi Adebisi Akinola⁴

Abstract

Purpose: To evaluate phytocompounds from Alstonia boonei as promising anti-malarial drug candidates and determine their interactions with a key Plasmodium falciparum protein. Methods: Gas chromatographic-mass spectrometry (GC-MS) was used to obtain Alstonia boonei compounds and a computational approach was utilized. Maestro Schrodinger Suite was used to perform molecular docking, prediction of absorption, distribution, metabolism and excretion (ADME) properties, molecular mechanics/generalized born surface area (MM/GBSA) estimation, induced-fit docking, and AutoQSAR analysis. These methods were employed to predict the binding efficacy and stability of Alstonia boonei-derived phytocompounds against Plasmodium falciparum dihydroorotate dehydrogenase protein using artemether as standard drug. Result: The results identified five phytocompounds: Sweroside (-10.152 kcal/mol), 7-Deoxyloganic acid (-10.066 kcal/mol), Swertiamarin (-9.611 kcal/mol), Secologanoside methyl ester (-9.013 kcal/mol), and Caffeic acid (-8.178 kcal/mol) with superior binding stability compared to the standard drug, artemether. These compounds also demonstrated a better induced fit docking score, indicating more favorable and stable interactions with the target protein. Conclusion: This work suggests that the five (5) identified phytocompounds from Alstonia boonei are effective potential inhibitors of Plasmodium falciparum dihydroorotate dehydrogenase and represent promising candidates for further development as anti-malarial treatments.