Author/Authors :
Monsefesfahani, Hamidreza Department of Pharmacognosy - Faculty of Pharmacy -Tehran University of Medical Sciences, Tehran, Iran , Moridi Farimani, Mahdi Department of Phytochemistry - Medicinal Plants and Drugs Research Institute - Shahid Beheshti University, Evin, Tehran, Iran , Nejad Ebrahimi, Samad Department of Phytochemistry - Medicinal Plants and Drugs Research Institute - Shahid Beheshti University, Evin, Tehran, Iran , Hyung Jung, Jee College of Pharmacy - Pusan National University, Busan, South Korea , Aliahmadi, Atousa Department of Biology - Medicinal Plants and Drugs Research Institute - Shahid Beheshti University, Evin, Tehran, Iran , Abbas-Mohammadi, Mahdi Department of Phytochemistry - Medicinal Plants and Drugs Research Institute - Shahid Beheshti University, Evin, Tehran, Iran , Skropeta, Danielle Molecular Horizons and School of Chemistry & Molecular Bioscience - University of Wollongong, NSW, Australia , Kazemian, Hossein Department of Microbiology - Faculty of Medicine - Ilam University of Medical Sciences, Ilam, Iran , Feizabadi, Mohammadmehdi Department of Microbiology - School of Medicine - Tehran University of Medical Sciences, Tehran, Iran , Miran, Mansour Department of Pharmacognosy and Biotechnology - School of Pharmacy - Ardabil University of Medical Sciences, Ardabil, Iran
Abstract :
Background: A bioassay-guided fractionation technique was used to evaluate the active
constituents of the perennial plant L. officinale W.D.J. Koch (Apiaceae) against multidrug
resistant (MDR) Mycobacterium tuberculosis.
Methods: Column chromatography was used to isolation of compounds from L. officinale and
spectroscopic methods including 1D and 2D NMR (Nuclear magnetic resonance) and HRMS
(high resolution mass spectrometry) were used to identification of the isolated compounds.
Also, to evaluate antibacterial activity, minimum inhibitory concentration (MIC) was carried
out by broth micro-dilution method. Finally, molecular docking (MD) was performed using the
Schrödinger package to evaluate interactions between the active compounds and InhA protein.
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), imperatorin
(5), ferulic acid (6) and falcarindiol (7). Falcarindiol and oxypeucedanin indicated a moderate
activity on MDR M. tuberculosis with MIC values of = 32 and 64 μg/mL, respectively.
Antibacterial activity of falcarindiol was also observed against S. aureus and methicillinresistant
S. aureus strains with the MIC values of 7.8 and 15.6 μg/mL, respectively. The results
of docking analysis showed a good affinity of oxypeucedanin (3) and falcarindiol (7) to InhA
enzyme with docking score values of -7.764 and -7.703 kcal/mol, respectively.
Conclusion: Finally, 7 compounds were isolated from L. officinale that compounds 2-6
report for the first time from this plant. On the basis of the molecular docking (MD) 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. Moreover, antibacterial activity of falcarindiol
against methicillin-resistant S. aureus (MRSA) was remarkable.
Keywords :
Antibacterial activity , Bioassay , guided fractionation , Levisticum officinale , Molecular docking , Multidrug resistance , Mycobacterium tuberculosis
