Gas Chromatography – Mass Spectrometry Analysis and in Silico Antimalarial Activity Studies of Compounds from Leaves Extracts of Mitragyna inermis (Willd.) Kuntze
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Date
2024-08-17
Journal Title
Journal ISSN
Volume Title
Publisher
Journal of Complementary and Alternative Medical Research
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.