Uncommon Chlorinated Xanthone and Other Antibacterial Compounds from the Lichen Cladonia incrassata

Abstract

Bioassay-guided fractionation of an extract of the lichen Cladonia incrassata against Staphylococcus aureus led to a novel compound, 1,5-dihydroxy-2,4,6-trichloro-7-methylxanthone (1), along with six known compounds: (−)-usnic acid (2), didymic acid (3), condidymic acid (4), squamatic acid (5), thamnolic acid (6), and prasinic acid (7). Didymic, condidymic, and prasinic acids were isolated for the first time from C. incrassata. Didymic, condidymic, and (−)-usnic acids were active against S. aureus (a minimum inhibitory concentration of 7.5 µg/mL).

Key words

xanthone - Cladonia incrassata - Cladionaceae - antibacterial - Staphylococcus aureus - structure elucidation

• References

• 1 Müller K. Pharmaceutically relevant metabolites from lichens. Appl Microbiol Biotechnol 2001; 56: 9-16
• 2 Ingólfsdóttir K. Molecules of interest: usnic acid. Phytochemistry 2002; 61: 729-736
• 3 Perry NB, Benn MH, Brennan NJ, Burgess EJ, Ellis G, Galloway DJ, Lorimer SD, Tangney RS. Antimicrobial, antiviral and cytotoxic activity of New Zealand lichens. Lichenologist 1999; 31: 627-636
• 4 Shukla V, Joshi GP, Rawat MSM. Lichens as a potential natural source of bioactive compounds: a review. Phytochem Rev 2010; 9: 303-314
• 5 Kortepeter SA. Lichen speciation in the section Cocciferae: Cladonia incrassata and Cladonia cristatella . J Undergrad Sci 1996; 3: 71-73
• 6 Kukwa M. The lichen species Cladonia incrassata (Lecanorales, Ascomycota Lichenisati) in Poland, and notes on C. anitae . Polish Bot J 2005; 50: 69-73
• 7 Culberson WL, Culberson CF, Johnson A. A new endemic red-fruited Cladonia from the North Carolina coast. Mycologia 1982; 74: 662-667
• 8 Huovinen K, Ahti T, Stenroos S. The composition and contents of aromatic lichen substances in Cladonia, section Cocciferae. Ann Bot Fennici 1989; 26: 133-148
• 9 Dieu A, Millot M, Champavier Y, Chulia AJ, Vergnaud J, Chaleix V, Bressollier P, Sol V, Gloaguen V. Antimicrobial activity of Cladonia incrassata acetone extract. Planta Med 2012; 78: 1247
• 10 European Directorate for the Quality of Medicines & Health Care. Efficacy of antimicrobial preservation (part 5.1.3.). European Pharmacopoeia, 8th ed. Technical tips online. Available at. http://online6.edqm.eu/ep800/# Accessed: December 19, 2013.
• 11 Ranković B, Kosanić M, Stanojković T, Vasiljević P, Manojlović N. Biological activities of Toninia candida and Usnea barbata together with their norstictic acid and usnic acid constituents. Int J Mol Sci 2012; 13: 14707-14722
• 12 Kosanić M, Ranković B, Stanojković T. Antioxidant, antimicrobial, and anticancer activities of three Parmelia species. J Sci Food Agric 2012; 92: 1909-1916
• 13 Burkholder PR, Evans AW, McVeigh I, Thornton HK. Antibiotic activity of lichens. Proc Natl Acad Sci U S A 1944; 30: 250-255
• 14 König GM, Wright AD. ¹H and ¹³C NMR and biological activity investigations of four lichen derived compounds. Phytochem Anal 1999; 10: 279-284
• 15 Huneck S, Yoshimura I. Identification of lichen substances. Heidelberg: Springer-Verlag; 1996: 219
• 16 Chester DO, Elix JA. Condidymic acid, a new dibenzofuran from the lichen Cladonia squamulosa . Aust J Chem 1981; 34: 1501-1506
• 17 Yoshimura I, Kinoshita Y, Yamamoto Y, Huneck S, Yamada Y. Analysis of secondary metabolites from lichen by high performance liquid chromatography with a photodiode array detector. Phytochem Anal 1994; 5: 197-205
• 18 Elix JA, Jones AJ, Lajide L, Coppins BJ, James PW. Two new diphenyl ethers and a new depside from the lichen Micarea prasina Fr. Aust J Chem 1984; 37: 2349-2364
• 19 Timdal E. The lichen genus Phyllopsora (Ramalinaceae) in the West Indies. Biblioth Lichenol 2011; 106: 319-351
• 20 Micheletti AC, Honda NK, Lima DP, Beatriz A, Santʼana MR, Carvalho NCP, Matos MFC, Queiróz LMM, Bogo D, Zorzatto JR. Chemical modifications of a natural xanthone and antimicrobial activity against multidrug resistant Staphylococcus aureus and cytotoxicity against human tumor cell lines. Quim Nova 2011; 34: 1014-1020
• 21 Hu LH, Yip SC, Sim KY. Xanthones from Hypericum ascyron . Phytochem 1999; 52: 1371-1373
• 22 Masters KS, Bräse S. Xanthones from fungi, lichens, and bacteria: the natural products and their synthesis. Chem Rev 2012; 112: 3717-3776
• 23 Elix JA, Crook CE. The joint occurrence of chloroxanthones in lichens, and a further thirteen new lichen xanthones. Bryologist 1992; 95: 52-64
• 24 Elix JA, Gaul KL, Jiang H. The structure and synthesis of some minor xanthones from the lichen Rinodina thiomela . Aust J Chem 1993; 46: 95-110
• 25 Lauterwein M, Oethinger M, Belsner K, Peters T, Marre R. In vitro activities of the lichen secondary metabolites vulpinic acid, (+)-usnic acid, and (−)-usnic acid against aerobic and anaerobic microorganisms. Antimicrob Agents Chemother 1995; 39: 2541-2543
• 26 Yilmaz M, Türk AÖ, Tay T, Kivanç M. The antimicrobial activity of extracts of the lichen Cladonia foliacea and its (−)-usnic acid, atranorin, and fumarprotocetraric acid constituents. Z Naturforsch 2004; 59c: 249-254
• 27 Yoshikawa K, Kokudo N, Tanaka M, Nakano T, Shibata H, Aragaki N, Higuchi T, Hashimoto T. Novel abietane diterpenoids and aromatic compounds from Cladonia rangiferina and their antimicrobial activity against antibiotics resistant bacteria. Chem Pharm Bull 2008; 56: 89-92
• 28 Chakor N, Patil G, Writer D, Periyasamy G, Sharma R, Roychowdhury A, Mishra PD. First total synthesis of prasinic acid and its anticancer activity. Bioorg Med Chem Lett 2012; 22: 6608-6610
• 29 Brodowski MH, White MG. Usnic acid deodorant stick. US Patent 5417962; 1995.
• 30 Aalto-Korte K, Lauerma A, Alanko K. Occupational allergic contact dermatitis from lichens in present-day Finland. Contact Dermatitis 2005; 52: 36-38
• 31 Mitchell JC. Stereoisomeric specificity of usnic acid in delayed hypersensitivity. J Invest Dermatol 1966; 47: 167-168
• 32 Santos NP, Nascimento SC, Silva JF, Pereira ECG, Silva NH, Honda NK, Santos-Magalhães NS. Usnic acid-loaded nanocapsules: an evaluation of cytotoxicity. J Drug Del Sci Tech 2005; 15: 355-361