Bioactive Constituents of Mitragyna inermis Leaves: GC-MSProfiling and In Silico Molecular Docking Studies againstMethicillin-Resistant Staphylococcus aureus (MRSA)

Abstract

The pervasive dissemination of Methicillin-Resistant Staphylococcus aureus (MRSA) underscores theurgent need for the identification of novel therapeutic agents, whether accompanied by side effects ornot. Mitragyna inermis, a plant revered in traditional Nigerian medicine, emerges as a promisingreservoir of antimicrobial compounds. The phytochemical constituents of an ethanol leaf extract of M.inermis were elucidated through Gas Chromatography-Mass Spectrometry (GC-MS). Moleculardocking studies were conducted against two pivotal MRSA targets: penicillin-binding protein 2a(PBP2a; PDB ID: 4CJN) and the tyrosine kinase domain (PDB ID: 1MWT), utilizing PyRx software.Ciprofloxacin served as a reference ligand. The drug-likeness and toxicity profiles of the top-scoringcompounds were predicted employing SwissADME and admetSAR. GC-MS analysis discerned 32distinct compounds, with cis-13,16-docosadienoic acid (12.33%) emerging as the most prevalent.Molecular docking revealed an array of compounds exhibiting robust binding affinities. Notably, (8Z)-1-oxacycloheptadec-8-en-2-one (LMI1) demonstrated the highest binding energy (-7.20 kcal/mol forboth protein targets), surpassing ciprofloxacin in its efficacy against 4CJN. ADMET predictionsindicated favorable drug-like characteristics for the majority of the leading compounds, although certainligands exhibited potential hepatotoxicity and carcinogenicity. M. inermis harbors bioactive compoundswith substantial binding affinity to MRSA-associated proteins. The in silico findings suggest that thesecompounds, particularly LMI1, represent promising candidates for anti-MRSA drug development andmerit further validation through in vitro and in vivo studies.