Evaluation and understanding the molecular basis of the antimethicillin-resistant Staphylococcus aureus activity of secondary metabolites isolated from Lamium amplexicaule

Background: The genus Lamium includes about forty annual or perennial plants distributed everywhere, it has significant biological activities including antimicrobial, antioxidant and antischistosomal effects. However, no detailed reports about the antimicrobial (Anti-MRSA) effect of the isolated metabolites. Objective: Studying the mechanism of action of the antimicrobial (Anti-MRSA) activity of the isolated metabolites. Materials and Methods: The EtOAc extract of L. amplexicaule was subjected to different chromatographic methods to isolate the secondary metabolites, and the isolated compounds were elucidated by spectroscopic techniques. The antimicrobial activity against strains of microorganisms was performed according to Minimum Inhibitory Concentration, the study of Anti-MRSA activity was explained by molecular docking against CrtM enzyme. Results: Phytochemical study of the aerial parts of L. amplexicaule resulted in the isolation of 5 known compounds; phytol (1), b‑sitosterol (2), isorhamnetin (3), 3,4‑dihydroxy‑methyl benzoate (4), and hydroxynervonic acid (5). The antimicrobial activity of the isolated metabolites revealed that compounds 1, 3, and 4 have pronounced antimethicillin‑resistant Staphylococcus aureus (MRSA) effect. Conclusion: These all known compounds were firstly isolated from L. amplexicaule. Three of them showed pronounced anti- MRSA effect, The mechanism of action against dehydrosqualene synthase enzyme was established. In addition, the study of molecular determinates of activity of these new scaffolds as anti‑MRSA has a great importance for the development of new anti‑MRSA candidates.