Gas Chromatography – Mass Spectrometry Analysis and in Silico Antimalarial Activity Studies of Compounds from Leaves Extracts of Mitragyna inermis (Willd.) Kuntze

Abstract

Background: Malaria remains the deadliest infectious diseases in many tropical and subtropical regions, including Nigeria and other West African countries where its transmission occurs all year round. In many inhabitants, medicinal plants are traditionally used as remedies against the symptoms of acute malaria because of their efficacious properties demonstrated by their phytoconstituents. Mitragyna inermis is one of the medicinal plants used by traditional healers in Nigeria for the treatment of various human diseases including malaria. Methods: We identified the phytochemical constituents of the methanol leaves extract of M.  Inermis using gas chromatography-mass spectrometry (GC-MS) technique. Furthermore, the in silico antimalarial study was conducted by investigating the binding interactions of the identified compounds with plasmepsin II, a key enzyme implicated in malaria pathogenesis using EH58 reference ligand by employing molecular docking techniques. Results: A total number of 40 compounds were identified from the extract of M.inermis, and cis-13,16-docasadienoic acid (12. 33 %) was identified as the major phytochemical. Other phytochemicals like Pyrrolo[1,2-a] pyazine-1,4-dione, hexahydro-3-(methylpropyl), 3-benzyl-6-methyl-2,5-piperazinedione, 2,5 dibenzyloxynitrobenzene, carbonic acid, 2-dimethylaminoethyl neopentyl ester were found but in trace amounts. The results of molecular docking studies predicted interactions of compounds from M. inermis with plasmepsin II enzyme. Five top-scoring bioactive compounds were selected based on their binding energies (docking scores) upon docking with target protein, with compound 2, (2,5-dibenzyloxynitrobenzene) exhibiting the best binding affinity. ADME properties indicated favorable drug-like characteristics for these compounds, while toxicity predictions showed hepatotoxicity and immunotoxicity. Pharmacokinetic assessments revealed high gastrointestinal absorption, blood-brain barrier permeability for compound 2, and inhibition potential against CYP enzymes for certain compounds, offering insights into their therapeutic potential against malaria. Conclusion: The molecular docking analysis revealed the potential of phytochemicals from M. inermis to interact effectively with plasmepsin II enzyme, showing promising antimalarial potentials. The identified compounds exhibited favorable drug-like properties and minimal toxicity concerns, highlighting their potential as candidates for further exploration in the development of antimalarial agents.