In vitro antituberculotic activity of several lichen metabolites

Current epidemiological evidence suggests that one-third of the world's population is infected with Mycobacterium tuberculosis with 8 million new cases and 2 million deaths per year. Lichens are symbiotic associations between a fungus and an alga, some of which (e.g. Iceland moss) have been known for antibiotic effects throughout the ages [1]. Earlier investigations published in the 1950s point to antimycobacterial potential of several pure lichen metabolites [2,3], however most of the studies have either involved other Mycobacterium species than M. tuberculosis, and/or the MIC values are missing. In the continuation of our search to identify natural products with antimycobacterial activity [4], we aimed to reinvestigate four commercially available lichen metabolites, (+)-usnic acid, evernic acid, psoromic acid and vulpic acid, for their in vitro antituberculotic effects. H₃₇Rv strain of Mycobacterium tuberculosis and the well-established microplate alamar blue assay (MABA) [5] were used for the determination of the MIC values. Rifampicin served as the reference drug (MIC: 0.07µg/ml). (+)-Usnic acid proved to be the most potent antituberculotic agent (MIC: 5.2µg/ml), followed by psoromic acid (MIC: 44µg/ml) and vulpic acid (MIC: 140µg/ml). Evernic acid was found to be inactive at highest concentrations tested (MIC: >200µg/ml). Ingolfsdottir and his coworkers have recently reported the antibiotic activity of usnic acid against Mycobacterium aurum, a non-pathogenic organism with a similar sensitivity profile to M. tuberculosis [6]. Hence, this is the first study reporting the growth inhibitory activity of all four compounds against the causative agent of pulmonary tubercle, M. tuberculosis. This presentation will deal with the in vitro antimycobacterial effects of these lichens metabolites. Possible biological target(s) of the compounds will also be discussed.

References: [1] Vartia, K.O. (1973) The Lichens. Academic Press, New York. 547–561. [2] Shibata, S. et al. (1948) Jap. Med. J. 1: 152–155. [3] Stoll, A. et al. (1950) Schweiz. Z. Path. Bakt. 13: 729–751. [4] Tasdemir, D. et al. (2006) Chem. Biodivers. 3: 1230–1237. [5] Collins, L., Franzblau, S.G. (1997) Antimicrob. Agents Chemother. 41: 1004–1009. [6] Ingolfsdottir, K. et al. (1998) Eur. J. Pharm. Sci. 6: 141–144.