Antibacterial Components of Levisticum officinale Koch Against Multidrug-resistant Mycobacterium tuberculosis

Background: Levisticum officinale commonly known as as Anjedan e roomi in the Persian language, is a member of the Apiaceae family. One of the most important biological activities reported to date for L. officinale is the antibacterial activity. So, a bioassay-guided fractionation technique was used to evaluate the active constituents of Levisticum officinale against some bacterial strains. Methods: Column chromatography was used to isolation of compounds from Levisticum officinale. Spectroscopic methods including 1D & 2D NMR and HRMS were used to identification of isolated compounds. Also to evaluate antibacterial activity, minimum inhibitory concentration (MIC) was carried out by broth micro-dilution method. Results: Phytochemical analysis of the ethyl acetate extract of the plant roots led to isolation of bergapten (1), isogosferol (2), oxypeucedanin (3), oxypeucedanin hydrate (4), oxyimperatorin (5), ferulic acid (6) and falcarindiol (7) that falcarindiol and oxypeucedanin were relatively active on MDR M. tuberculosis with MIC values of = 32 and 64 μg/mL, respectively. The results of the docking analysis showed that oxypeucedanin (3) and falcarindiol (7) had good affinity for InhA with docking score values of -7.764 and -7.703 kcal/mol, respectively. Also, compounds 3 and 7 were studied against two Gram negative (Escherichia coli, Pseudomonas aeruginosa) and two Gram positive (Staphylococcus aureus and Enterococcus faecium) bacteria strains. Falcarindiol showed antibacterial activity against the S. aureus strain with a MIC value of 7.8 μg/mL and against methicillin-resistant S. aureus (MRSA), with a MIC value of 15.6 μg/mL. Conclusion: Finally, 7 compounds were isolated that compounds 2-6 report for the first time from Levisticum officinale. On the basis of the molecular docking study, oxypeucedanin (3) and falcarindiol (7) as active compounds against M. tuberculosis may be proposed as potential inhibitors of 2-trans-enoyl-ACP reductase (InhA), a key enzyme involved in the biosynthesis of the mycobacterial cell wall.