Characterisation of Bioactive Compounds in Morinda lucida Root Extracts and Their Molecular Docking Interactions with Plasmodium falciparum Dihydrofolate Reductase

Morinda lucida, locally referred to as oruwo among the Yoruba of South West Nigeria, is a medicinal tree whose root extracts are traditionally employed against malaria, jaundice, and febrile conditions. Despite documented ethnomedicinal relevance, the specific bioactive compounds and their molecular interactions with antimalarial drug targets remain incompletely characterised. This study isolated and characterised bioactive compounds from methanol root extracts of M. lucida obtained from Ekiti State, and evaluated their binding affinity against Plasmodium falciparum dihydrofolate reductase using molecular docking simulation. Column chromatography and preparative TLC were used for compound isolation. Structure elucidation was performed by NMR spectroscopy and mass spectrometry. In silico molecular docking was conducted using AutoDock Vina against the crystal structure of PfDHFR obtained from the Protein Data Bank. Three major compounds were isolated and identified as lucidin, alizarin, and nordamnacanthal, all belonging to the anthraquinone class. Molecular docking revealed that alizarin demonstrated the highest binding affinity at negative 7.8 kcal/mol, comparable to the reference antifolate pyrimethamine at negative 7.4 kcal/mol. Key binding interactions occurred at the active site residues Asp54 and Ile164. These computational findings, supported by phytochemical characterisation, nominate anthraquinone constituents of M. lucida as candidate antimalarial leads warranting further in vitro and in vivo pharmacological evaluation. Keywords: Morinda lucida, anthraquinones, molecular docking, Plasmodium falciparum DHFR, antimalarial.