Lichenochemicals: extraction, purification, characterization, and application as potential anticancer agents

References

• Clark A. Natural product as a resource for new drugs. Pharma Res. 1966;13(8):1133–1141.
   Google Scholar
• Salehi B, Sharif-Rad J, Seca AML, et al. Current trends on seaweeds: looking at chemical composition, phytopharmacology, and cosmetic applications. Molecules. 2019;24(22):4182:1–50.
   Web of Science ®Google Scholar
• Sharif-Rad J, Ozleyen A, Tumer TB, et al. Natural products and synthetic analogs as a source of antitumor drugs. Biomolecul. 2019;9(11):679: 1–52.
   Web of Science ®Google Scholar
• Salehi B, Ata A, Kumar NVA, et al. Antidiabetic potential of medicinal plants and their active components. Biomolecul. 2019;9(10):551: 1–121.
   Web of Science ®Google Scholar
• Cragg GM, Pezzuto JM. Natural products as a vital source for the discovery of cancer chemotherapeutic and chemopreventive agents. Med Princ Pract. 2016;25(2): 41–59.
   Google Scholar
• Newman DJ, Cragg GM. Natural products as sources of new drugs from 1981 to 2014. J Nat Prod. 2016;79:629–661.
   PubMed Web of Science ®Google Scholar
• Shrestha G, St. Clair LL. Lichens: A promising source of antibiotic and anticancer drugs. Phytochem Rev. 2013;12(1):229–244.
   Web of Science ®Google Scholar
• Zambare VP, Christopher LP. Biopharmaceutical potential of lichens. Pharm Biol. 2012;50(6):778–798.
   PubMed Web of Science ®Google Scholar
• Shukla V, Joshi GP, Rawat MSM. Lichens as a potential natural source of bioactive compounds: A review. Phytochem Rev. 2010;9(2):303–314.
   Web of Science ®Google Scholar
• Seymour FA, Crittenden PD, Dickinson MJ, et al. Breeding systems in the lichen-forming fungal genus Cladonia. Fungal Genet Biol. 2005;42(6):554–563.
   PubMed Web of Science ®Google Scholar
• Sipman H, Aptroot A. Where are the missing lichens? Mycol Res. 2001;105(12):1433–1439.
   Google Scholar
• Kosanić M, Ranković B, Stanojković T, et al. Cladonia lichens and their major metabolites as possible natural antioxidant, antimicrobial and anticancer agents. LWT - Food Sci Technol. 2014;59(1):518–525.
   Web of Science ®Google Scholar
• Bačkorová M, Jendzˇelovsky´R, Kello M, et al. Lichen secondary metabolites are responsible for induction of apoptosis in HT-29 and A2780 human cancer cell lines. Toxicol Vitr. 2012;26(3):462–468.
   PubMed Web of Science ®Google Scholar
• Bézivin C, Tomasi S, Lohezic-Le Devehat F, et al. Cytotoxic activity of some lichen extracts on murine and human cancer cell lines. Phytomed. 2003;10(6–7):499–503.
   PubMed Web of Science ®Google Scholar
• Suh SS, Kim TK, Kim JE, et al. Anticancer activity of ramalin, a secondary metabolite from the antarctic lichen Ramalina terebrata, against colorectal cancer cells. Molecule. 2017;22(1361):1–12.
   Google Scholar
• Dayan N, Kromidas L. Formulating, packaging, and marketing of natural cosmetic products. New Jerssy (USA): John Wiley & Sons, Ltd; 2011.
   Google Scholar
• Komaty S, Letertre M, Dang HD, et al. Sample preparation for an optimized extraction of localized metabolites in lichens: application to Pseudevernia furfuracea. Talanta. 2016;150:525–530.
   PubMed Web of Science ®Google Scholar
• Cardile V, Graziano ACE, Avola R, et al. Potential anticancer activity of lichen secondary metabolite physodic acid. Chem Biol Interact. 2017;263:36–45.
   PubMed Web of Science ®Google Scholar
• Paluszczak J, Kleszcz R, Studzińska-Sroka E, et al. Lichen-derived caperatic acid and physodic acid inhibit Wnt signaling in colorectal cancer cells. Mol Cell Biochem. 2018;441(1–2):109–124.
   PubMed Web of Science ®Google Scholar
• Russo A, Piovano M, Lombardo L, et al. Lichen metabolites prevent UV light and nitric oxide-mediated plasmid DNA damage and induce apoptosis in human melanoma cells. Life Sci. 2008;83(13–14):468–474.
   PubMed Web of Science ®Google Scholar
• Ranković B. Lichen secondary metabolites: bioactive properties and pharmaceutical potential. London (UK): Springer; 2015. p. 1–202.
   Google Scholar
• Ramawat KG, Merillon JM. Biotechnology : secondary metabolites : plants and microbes. Enfield (New Hampshire): Science Publishers; 2007.
   Google Scholar
• Molnár K, Farkas E. Current results on biological activities of lichen secondary metabolites: A review. Zeitschrift fur Naturforschung J Biosci. 2010;65:157–173.
   PubMed Web of Science ®Google Scholar
• Boustie J, Grube M. Lichens—a promising source of bioactive secondary metabolites. Plant Genet Resour Charact Util. 2005;3(2):273–287.
   Google Scholar
• Culberson CF, Culberson WL. Future directions in lichen chemistry. Bryologist. 2001;104(2):230–234.
   Web of Science ®Google Scholar
• Solár P, Hrčková G, Koptašíková L, et al. Murine breast carcinoma 4T1 cells are more sensitive to atranorin than normal epithelial NMuMG cells in vitro: anticancer and hepatoprotective effects of atranorin in vivo. Chem Biol Interact. 2016 Apr 25;250:27–37.
   PubMed Web of Science ®Google Scholar
• Talapatra SK, Rath O, Clayton E, et al. Depsidones from lichens as natural product inhibitors of M - phase phosphoprotein 1, a human kinesin required for cytokinesis. J Nat Prod. 2016;79(6):1576–1585.
   PubMed Web of Science ®Google Scholar
• Zakharenko A, Luzina O, Koval O, et al. Tyrosyl-DNA phosphodiesterase 1 inhibitors: usnic acid enamines enhance the cytotoxic effect of camptothecin. J Nat Prod. 2016;79(11):2961–2967.
   PubMed Web of Science ®Google Scholar
• O’Neill MA, Mayer MM, Murray KE, et al. Does usnic acid affect microtubules in human cancer cells? Brazilian J Biol. 2010;70(3):659–664.
   PubMed Web of Science ®Google Scholar
• Su Z-Q, Liu Y-H, Guo H-Z, et al. Effect-enhancing and toxicity-reducing activity of usnic acid in ascitic tumor-bearing mice treated with bleomycin. Int Immunopharmacol. 2017;46:146–155.
   PubMed Web of Science ®Google Scholar
• Yang Y, Park S-Y, Nguyen TT, et al. Lichen secondary metabolite, physciosporin, inhibits lung cancer cell motility. PLoS One. 2015;10(9):e0137889.
   PubMed Web of Science ®Google Scholar
• Upreti DK, Divakar PK, Shukla V, et al. Recent advances in lichenology: modern methods and approaches in lichen systematics and culture techniques. New Delhi (India): Springer; 2015. p. 2.
   Google Scholar
• Yang Y, Bhosle SR, Yu YH, et al. Tumidulin, a lichen secondary metabolite, decreases the stemness potential of colorectal cancer cells. Molecules. 2018;23(2968):1–13.
   Google Scholar
• Zhou R, Yang Y, Park S, et al. The lichen secondary metabolite atranorin suppresses lung cancer cell motility and tumorigenesis. Sci Rep. 2017; 7(1):1–13.
   PubMedGoogle Scholar
• Kumar J, Dhar P, Tayade AB, et al. Antioxidant capacities, phenolic profile and cytotoxic effects of saxicolous lichens from trans-Himalayan cold desert of Ladakh. PLoS One. 2014;9(6):e98696.
   PubMed Web of Science ®Google Scholar
• Nguyen DMT, Do LMT, Nguyen VT, et al. Phenolic compounds from the lichen Lobaria orientalis. J Nat Prod. 2017;80(2):261–268.
   PubMed Web of Science ®Google Scholar
• Delebassée S, Mambu L, Pinault E, et al. Fitoterapia cytochalasin E in the lichen Pleurosticta acetabulum. Anti-proliferative activity against human HT-29 colorectal cancer cells and quantitative variability. Fitoterapia. 2017;121(May):146–151.
   PubMedGoogle Scholar
• Nguyen TT, Yoon S, Yang Y, et al. Lichen secondary metabolites in Flavocetraria cucullata exhibit anti-cancer effects on human cancer cells through the induction of apoptosis and suppression of tumorigenic potentials. PLoS One. 2014;9:10.
   Web of Science ®Google Scholar
• Calcott MJ, Ackerley DF, Knight A, et al. Secondary metabolism in the lichen symbiosis. Chem Soc Rev. 2018;47(5):1730–1760.
   PubMed Web of Science ®Google Scholar
• Zhang BW, Xu JL, Zhang H, et al. Structure elucidation of a polysaccharide from Umbilicaria esculenta and its immunostimulatory activity. Plos One. 2016;11(2):e01168472.
   Google Scholar
• Manojlović N, Ranković B, Kosanić M, et al. Chemical composition of three Parmelia lichens and antioxidant, antimicrobial and cytotoxic activities of some their major metabolites. Phytomed. 2012;19(13):1166–1172.
   PubMed Web of Science ®Google Scholar
• Huneck S, Yoshimura I. Data of lichen substances. In: Identification of lichen substances. Berlin (Heidelberg): Springer; 1996. p. 125–446.
   Google Scholar
• Feige GB, Lumbsch HT. Identification of lichen substances by a standardized liquid chromatographic method. J Chromat Method A. 1993;646:417–427.
   Web of Science ®Google Scholar
• Plsíkova J, Stepankova J, Kasparkova J, et al. Lichen secondary metabolites as DNA-interacting agents. Toxicol Vitr. 2014;28(2):182–186.
   PubMed Web of Science ®Google Scholar
• Galindo JLG, García BF, Torres A, et al. The joint action in the bioactivity studies of antarctic lichen Umbilicaria antarctica: synergic-biodirected isolation in a preliminary holistic ecological study. Phytochem Lett. 2016;20:433–442.
   Web of Science ®Google Scholar
• Goga M, Elečko J, Marcinčinová M, et al. Lichen metabolites: an overview of some secondary metabolites and their biological potential. Switzerland: Springer; 2018.p. 1–36
   Google Scholar
• Molnár K, Farkas E. Biological activities of secondary lichen metabolites. Hungary; 2009. http://www.zpok.zoldpok.hu/img_upload/c1ed1e710aa1f4ec96d01e3f84439473/09_Molnar_Katalin_english.pdf
   Google Scholar
• Yousuf S, Choudhary MI, Atta UR. Lichens: chemistry and biological activities. In: UR, editor. Atta studies in Natprod Chem. UK: Oxford. 2014. p. 223–259.
   Google Scholar
• Stocker-Wörgötter E. Metabolic diversity of lichen-forming ascomycetous fungi: culturing, polyketide and shikimate metabolite production, and PKS genes. Nat Prod Rep. 2008;25(1):188–200.
   PubMed Web of Science ®Google Scholar
• Huneck S. The significance of lichens and their metabolites. Naturwissenschaften. 1999;86(12):559–570.
   PubMed Web of Science ®Google Scholar
• Dembitsky V. Lichen secondary metabolites: lichens as a potential source of bioactive secondary metabolites. Switzerland: Springer International Publishing; 2015. p. 1–29
   Google Scholar
• Edwards HGM, Newton EM, Wynn-Williams DD. Molecular structural studies of lichen substances II: atranorin, gyrophoric acid, fumarprotocetraric acid, rhizocarpic acid, calycin, pulvinic dilactone and usnic acid. J Mol Struct. 2003;651–653:27–37.
   Web of Science ®Google Scholar
• Edwards HGM, Newton EM, Wynn-Williams DD, et al. Molecular spectroscopic studies of lichen substances 1: parietin and emodin. J Mol Struct. 2003;648(1–2):49–59.
   Web of Science ®Google Scholar
• Gasulla F, Herrero JEsteban-Carrasco A, et al. Photosynthesis in lichen: light reactions and protective mechanisms. In: Advances in Photosynthesis - Fundamental Aspects (ed. Najafpour MM), IntechOpen, 2012;149–174.
   Google Scholar
• Smith VR, Gremmen NJM. Photosynthesis in a sub-Antarctic shore-zone lichen. New Phytol. 2001;149(2):291–299.
   Web of Science ®Google Scholar
• Zeytinoglu H, Incesu Z, Ayaz Tuylu B, et al. Determination of genotoxic, antigenotoxic and cytotoxic potential of the extract from lichen Cetraria aculeata (Schreb.) Fr. in vitro. Phyther Res. 2008;22(1):118–123.
   PubMed Web of Science ®Google Scholar
• Zlatanovic I, Petrovic G, Jovanovic O, et al. Isolation and identification of secondary metabolites of Umbilicaria crustulosa (Ach.) frey. Facta Univ Ser Phys Chem Technol. 2016;14(2):125–133.
   Google Scholar
• Zugic A, Jeremic I, Isakovic A, et al. Evaluation of anticancer and antioxidant activity of a commercially available CO2 supercritical extract of old man’s beard (Usnea barbata). PLoS One. 2016;11(1):1–14.
   Web of Science ®Google Scholar
• Manojlovic NT, Vasiljevic PJ, Maskovic PZ, et al. Chemical composition, antioxidant, and antimicrobial activities of lichen Umbilicaria cylindrica (L.) delise (Umbilicariaceae). Evidence Based Complement Altern Med. 2012;2012:1–8.
   Web of Science ®Google Scholar
• Bessadóttir M, Skúladóttir E, Gowan S, et al. Effects of anti-proliferative lichen metabolite, protolichesterinic acid on fatty acid synthase, cell signalling and drug response in breast cancer cells. Phytomedicine. 2014;21(12):1717–1724.
   PubMed Web of Science ®Google Scholar
• Ristic S, Rankovic B, Kosanić M, et al. Biopharmaceutical potential of two Ramalina lichens and their metabolites. Curr Pharm Biotechnol. 2016;17(7):651–658.
   PubMed Web of Science ®Google Scholar
• Shang J, Fang M, Zhang L, et al. Purification and activity characterization of polysaccharides in the medicinal lichen Umbilicaria tornata from Taibai Mountain, China. Glycoconj J. 2018;35(1):107–117.
   PubMed Web of Science ®Google Scholar
• Azmir J, Zaidul ISM, Rahman MM, et al. Techniques for extraction of bioactive compounds from plant materials: A review. J Food Eng. 2013;117(4):426–436.
   Web of Science ®Google Scholar
• Yeash EA, Letwin L, Malek L, et al. Biological activities of undescribed North American lichen species. J Sci Food Agric. 2017;97(14):4721–4726.
   PubMed Web of Science ®Google Scholar
• Roullier C, Chollet-Krugler M, Van de Weghe P, et al. A novel aryl-hydrazide from the marine lichen Lichina pygmaea: isolation, synthesis of derivatives, and cytotoxicity assays. Bioorg Med Chem Lett. 2010;20(15):4582–4586.
   PubMed Web of Science ®Google Scholar
• Pejin B, Iodice C, Bogdanović G, et al. Stictic acid inhibits cell growth of human colon adenocarcinoma HT-29 cells. Arab J Chem. 2017;10:S1240–1242.
   Web of Science ®Google Scholar
• Studzińska-Sroka E, Piotrowska H, Kucińska M, et al. Cytotoxic activity of physodic acid and acetone extract from Hypogymnia physodes against breast cancer cell lines. Pharm Biol. 2016;54(11):2480–2485.
   PubMed Web of Science ®Google Scholar
• Singh AK. Hydrolytic maceration, expression and cold fat extraction. In: Extraction technologies for medicinal and aromatic plants. Trieste (Italy): ICS-UNIDO; 2008. p. 83–84.
   Google Scholar
• Basile A, Rigano D, Loppi S, et al. Antiproliferative, antibacterial and antifungal activity of the lichen Xanthoria parietina and its secondary metabolite parietin. Int J Mol Sci. 2015;16(4):7861–7875.
   PubMed Web of Science ®Google Scholar
• Fernández-Moriano C, González-Burgos E, Divakar PK, et al. Evaluation of the antioxidant capacities and cytotoxic effects of ten Parmeliaceae lichen species. Evid Based Complement Altern Med. 2016;2016:1–11.
   Google Scholar
• Duval J, Pecher V, Poujol M, et al. Research advances for the extraction, analysis and uses of anthraquinones: A review. Ind Crops Prod. 2016;94:812–833.
   Web of Science ®Google Scholar
• De Castro ML, Garcıa-Ayuso LE. Soxhlet extraction of solid materials: an outdated technique with a promising innovative future. Anal Chim Acta. 1998;369:1–10.
   Web of Science ®Google Scholar
• Alara OR, Abdurahman NH, Ukaegbu CI. Soxhlet extraction of phenolic compounds from Vernonia cinerea leaves and its antioxidant activity. J Appl Res Med Aromat Plants. 2018;11:12–17.
   Web of Science ®Google Scholar
• Mishra BB, Kishore N, Tiwari VK, et al. A novel antifungal anthraquinone from seeds of aegle marmelos correa (family Rutaceae). Fitoterapia. 2010;81(2):104–107.
   PubMed Web of Science ®Google Scholar
• Bayir Y, Odabasoglu F, Cakir A, et al. The inhibition of gastric mucosal lesion, oxidative stress and neutrophil-infiltration in rats by the lichen constituent diffractaic acid. Phytomed. 2006;13(8):584–590.
   PubMed Web of Science ®Google Scholar
• Melo MGD, Dos Santos JPA, Serafini MR, et al. Redox properties and cytoprotective actions of atranorin, a lichen secondary metabolite. Toxicol Vitr. 2011;25(2):462–468.
   PubMed Web of Science ®Google Scholar
• Kosanić M, Manojlović N, Janković S, et al. Evernia prunastri and Pseudoevernia furfuraceae lichens and their major metabolites as antioxidant, antimicrobial and anticancer agents. Food Chem Toxicol. 2013;53:112–118.
   PubMed Web of Science ®Google Scholar
• Chahra D, Ramdani M, Lograda T, et al. Chemical composition and antimicrobial activity of Evernia prunastri and Ramalina farinacea from Algeria. Issues Biol Sci Pharm Res. 2016;4(5):35–42.
   Google Scholar
• Kaufmann B, Christen P. Recent extraction techniques for natural products: microwave-assisted extraction and pressurised solvent extraction. Phytochem Anal. 2002;13(2):105–113.
   PubMed Web of Science ®Google Scholar
• Rostango MA, Prado JM. Natural product extraction: principles and applications. Cambridge (UK): Royal Society of Chem; 2013.
   Google Scholar
• Wang L, Weller CL. Recent advances in extraction of nutraceuticals from plants. Trends Food Sci Technol. 2006;17(6):300–312.
   Web of Science ®Google Scholar
• Arvindekar AU, Laddha KS. An efficient microwave-assisted extraction of anthraquinones from Rheum emodi: optimisation using RSM, UV and HPLC analysis and antioxidant studies. Ind Crops Prod. 2016;83:587–595.
   Web of Science ®Google Scholar
• Hemwimon S, Pavasant P, Shotipruk A. Microwave-assisted extraction of antioxidative anthraquinones from roots of Morinda citrifolia. Sep Purif Technol. 2007;54(1):44–50.
   Web of Science ®Google Scholar
• Dean JR. Extraction methods for environmental analysis. Chichester (UK): John Wiley and Sons; 1998.
   Google Scholar
• Eskilsson SC, Björklund E. Analytical-scale microwave-assisted extraction. J Chromatogr A. 2000;902(1):227–250.
   PubMed Web of Science ®Google Scholar
• Brachet A, Christen P, Veuthey JL. Focused microwave-assisted extraction of cocaine and benzoylecgonine from coca leaves. Phytochem Anal. 2002;13(3):162–169.
   PubMed Web of Science ®Google Scholar
• Bonny S, Paquin L, Carrié D, et al. Ionic liquids based microwave-assisted extraction of lichen compounds with quantitative spectrophotodensitometry analysis. Anal Chim Acta. 2011;707(1–2):69–75.
   PubMed Web of Science ®Google Scholar
• Paquin L, Gauffre F, Tomasi S. Ionic liquids coupled to microwave irradiation: an Efficient and selective process for secondary lichens metabolites extraction. Paper presented at: 1st international electronic conference on medicinal chemistry; 2015 November 2–27.
   Google Scholar
• Azwanida N. A review on the extraction methods use in medicinal plants, principles, strength and limitation. Med Aromat Plants. 2015;4(3):e1000196.
   Google Scholar
• Trojanowska A, Tsibranska I, Dzhonova D, et al. Ultrasound-assisted extraction of biologically active compounds and their successive concentration by using membrane processes. Chem Eng Res Des. 2019;147:378–389.
   Web of Science ®Google Scholar
• Ginsburg E, Kinsley MD, Quitral A. The power of ultrasound. Adm Radiol J. 1998;17(5):17–20.
   PubMedGoogle Scholar
• Chemat S, Lagha A, AitAmar H, et al. Comparison of conventional and ultrasound-assissted extraction of carvone and limonene from caraway seeds. Flavour Fragr J. 2004;19(3):188–195.
   Web of Science ®Google Scholar
• Sališová M, Toma Š, Mason TJ. Comparison of conventional and ultrasonically assisted extractions of pharmaceutically active compounds from Salvia officinalis. Ultrason Sonochem. 1997;4(2):131–134.
   PubMed Web of Science ®Google Scholar
• Sihvonen M, Järvenpää E, Hietaniemi V, et al. Advances in supercritical carbon dioxide technologies. Trends Food Sci Technol. 1999;10(6):217–222.
   Web of Science ®Google Scholar
• Zizovic I, Ivanovic J, Misic D, et al. SFE as a superior technique for isolation of extracts with strong antibacterial activities from lichen usnea barbata L. J Supercrit Fluids. 2012;72:7–14.
   Web of Science ®Google Scholar
• Poiana M, Sicari V, Mincione B. Supercritical carbon dioxide (SC-CO2) extraction of grapefruit flavedo. Flavour Fragr J. 1998;13(2):125–130.
   Web of Science ®Google Scholar
• Nieto A, Borrull F, Pocurull E, et al. Pressurized liquid extraction: A useful technique to extract pharmaceuticals and personal-care products from sewage sludge. Trends Anal Chem. 2010;29:752–764.
   Web of Science ®Google Scholar
• Mustafa A, Turner C. Pressurized liquid extraction as a green approach in food and herbal plants extraction: A review. Anal Chim Acta. 2011;703:8–18.
   PubMed Web of Science ®Google Scholar
• Luthria DL. Influence of experimental conditions on the extraction of phenolic compounds from parsley (Petroselinum crispum) flakes using a pressurized liquid extractor. Food Chem. 2008;107:745–752.
   Web of Science ®Google Scholar
• Sowbhagya HB, Chitra VN. Enzyme-assisted extraction of flavorings and colorants from plant materials. Crit Rev Food Sci Nutr. 2010;50(2):146–161.
   PubMed Web of Science ®Google Scholar
• Ahmad MR, Ismail M, Kadir A Proceedings of the international colloquium in textile engineering, fashion, apparel and design (ICTEFAD 2014); 2014.
   Google Scholar
• Saltan G, Bahadr Z. Chromatography and its applications: column chromatography for terpenoids and flavonoids. London: ItechOpen; 2012.
   Google Scholar
• Xiang Y, Jing Z, Haixia W, et al. Antiproliferative activity of phenylpropanoids isolated from Lagotis brevituba maxim. Phyther Res. 2017;31(10):1509–1520.
   PubMed Web of Science ®Google Scholar
• Perico-Franco LS, Soriano-garcía M, Cerbón MA, et al. Secondary metabolites and cytotoxic potential of Lobariella pallida and Stereocaulon strictum var. compressum, two lichens from Colombian páramo region. UK J Pharm Biosci. 2015;3(4):31–38.
   Google Scholar
• Duong T-H, Chavasiri W, Boustie J, et al. New meta-depsidones and diphenyl ethers from the lichen Parmotrema tsavoense (Krog & Swinscow) Krog & Swinscow, Parmeliaceae. Tetrahedron. 2015;71(52):9684–9691.
   Web of Science ®Google Scholar
• Le PP, Le LAC, Siva B, et al. Minor pyranonaphthoquinones from the apothecia of the lichen Ophioparma ventosa. J Nat Prod. 2016;79(4):1005–1011.
   PubMed Web of Science ®Google Scholar
• Garg A. Antimicrobial and anticancer properties of methyl-beta-orcinolcarboxylate from lichen (Evernia strumcirrhatum). National center for biotechnology information. PubChem Database. Patent=US2004198815, https://pubchem.ncbi.nlm.nih.gov/patent/US2004198815.2013.
   Google Scholar
• Wu S, Zhao Z, Okada Y, et al. Physiological activity of Chinese lichen (Gyrophora esculenta) component, methyl 2,4-dihydroxy-6-methylbenzoate and the related compounds. Asian J Chem. 2014;26(3):702–708.
   Google Scholar
• Fazio AT, Adler MT, Bertoni MD, et al. Lichen secondary metabolites from the cultured lichen mycobionts of Teloschistes chrysophthalmus and Ramalina celastri and their antiviral activities. Zeitschrift fur Naturforsch J Biosci. 2007;62(7–8):543–549.
   PubMed Web of Science ®Google Scholar
• Baena A, Gomez L, Gomez WA, et al. Murine invariant natural killer T cells recognize glycolipids derived from extracts of the lichen Stereocaulon ramulosum. Rev Vitae. 2015;22(1):13–26.
   Google Scholar
• Shrestha G, El-Naggar AM, St. Clair LL, et al. Anticancer activities of selected species of North American lichen extracts. Phyther Res. 2015;29(1):100–107.
   PubMed Web of Science ®Google Scholar
• Gonçalves JP, Martins MCB, Buril MDLL, et al. Antineoplastic activity and genotoxicity of organic extracts and barbatic acid isolated from the lichen Cladonia salzmannii Nyl. Int Arch Med. 2018;11(53):1–12.
   Google Scholar
• Millot M, Di Meo F, Tomasi S, et al. Photoprotective capacities of lichen metabolites: a joint theoretical and experimental study. J Photochem Photobiol B Biol. 2012;111:17–26.
   PubMed Web of Science ®Google Scholar
• Aravind SR, Sreelekha TT, Dileep Kumar BS, et al. Characterization of three depside compounds from a Western Ghat lichen Parmelia erumpens kurok with special reference to antimicrobial and anticancer activity. RSC Adv. 2014;4(65):34632–34643.
   Web of Science ®Google Scholar
• Galanty A, Koczurkiewicz P, Wnuk D, et al. Usnic acid and atranorin exert selective cytostatic and anti-invasive effects on human prostate and melanoma cancer cells. Toxicol In Vitr. 2017;40:161–169.
   PubMed Web of Science ®Google Scholar
• Liu Y, Guo M. Chemical proteomic strategies for the discovery and development of anticancer drugs. Proteomics. 2014;14(4–5):399–411.
   PubMed Web of Science ®Google Scholar
• Pol CS, Savale SA, Khare R, et al. Antioxidative, cardioprotective, and anticancer potential of two lichenized fungi, Everniastrum cirrhatum and Parmotrema reticulatum, from Western ghats of India. J Herbs Spices Med Plants. 2017;23(2):142–516.
   Google Scholar
• Nussbaumer S, Bonnabry P, Veuthey J, et al. Analysis of anticancer drugs : A review. Talanta. 2011;85(5):2265–8229.
   PubMed Web of Science ®Google Scholar
• Brusotti G, Cesari I, Dentamaro A, et al. Isolation and characterization of bioactive compounds from plant resources : the role of analysis in the ethnopharmacological approach. J Pharma Biomed Anal. 2014;87:218–228.
   PubMed Web of Science ®Google Scholar
• Ren MR, Hur J-S, Kim JY, et al. Anti-proliferative effects of Lethariella zahlbruckneri extracts in human HT-29 human colon cancer cells. Food Chem Toxicol. 2009;47(9):2157–2162.
   PubMed Web of Science ®Google Scholar
• Řezanka T, Dembitsky V. Novel brominated lipidic compounds from lichens of Central Asia. Phytochem. 1999;51(8):963–968.
   PubMed Web of Science ®Google Scholar
• Posokhov Y, Erten Ş, Koz Ö, et al. UV/VIS spectral properties of novel natural products from Turkish lichens. Int J Photoen. 2005;7(1):27–35.
   Web of Science ®Google Scholar
• Sasidharan S, Chen Y, Saravanan D, et al. Extraction, isolation and characterization of bioactive compounds from plant’s extracts. Afr J Tradit Complement Altern Med. 2011;8(1):1–10.
   PubMed Web of Science ®Google Scholar
• Revathy M, Sathya S, Manimekala NA. Preliminary phytochemical investigation and antibacterial effects of lichen Parmotrema perlatum against human pathogenes. Eur J Biomed Pharm Sci. 2015;2(4):336–347.
   Google Scholar
• Da Silva L, Roman-Campos D, de Vasconcelos C, et al. (+)-usnic acid isolated from the lichen Cladonia substellata impairs myocardial contractility. Planta Medica Int Open. 2017;4(2):59–65.
   Google Scholar
• Takenaka Y, Tanahashi T, Nagakura N. Three isocoumarins and a benzofuran from the cultured lichen mycobionts of Pyrenula sp. 2004;65:3119–3123.
   Google Scholar
• Liao C, Piercey-Normore MD, Sorensen JL, et al. In situ imaging of usnic acid in selected Cladonia spp. by vibrational spectroscopy. Analyst. 2010;135(12):3242–3248.
   PubMed Web of Science ®Google Scholar
• Tanahashi T, Takenaka Y, Ikuta Y, et al. Xanthones from the cultured lichen mycobionts of Pyrenula japonica and Pyrenula pseudobufonia. Phytochem. 1999;52(3):401–405.
   Web of Science ®Google Scholar
• Santos LS, Camarantin P, Mirabal- Y, et al. Chemotaxonomic through MALDI spectrometry fingerprinting of and electrospray chilean lichens ionization mass. Braz Arch Biol Technol. 2013;58(2):244–253.
   Web of Science ®Google Scholar
• Parrot D, Intertaglia L, Grube M, et al. Cyaneodimycin, a bioactive compound isolated from the culture of Streptomyces cyaneofuscatus associated with Lichina confinis. Eur J Org Chem. 2016;2016(23):3977–3982.
   Web of Science ®Google Scholar
• Leela K, Anchana Devi C. Isolation, purification and application of secondary metabolites from lichen Parmelia Perlata. Biosci Biotechnol Res Asia. 2017;14(4):1413–1428.
   Google Scholar
• Bazin M-A, Lamer A-CL, Delcros J-G, et al. Synthesis and cytotoxic activities of usnic acid derivatives. Bioorg Med Chem. 2008;16(14):6860–6866.
   PubMed Web of Science ®Google Scholar
• Russo A, Piovano M, Lombardo L, et al. Pannarin inhibits cell growth and induces cell death in human prostate carcinoma DU-145 cells. Anticancer Drugs. 2006;17(10):1163–1169.
   PubMed Web of Science ®Google Scholar
• Ari F, Celikler S, Oran S, et al. Genotoxic, cytotoxic, and apoptotic effects of Hypogymnia physodes (L.) Nyl. on breast cancer cells. Environ Toxicol. 2014;29(7):804–813.
   PubMed Web of Science ®Google Scholar
• Schinkovitz A, Kaur A, Urban E, et al. Cytotoxic constituents from lobaria scrobiculata and a comparison of two bioassays for their evaluation. J Nat Prod. 2014;77(4):1069–1073.
   PubMed Web of Science ®Google Scholar
• Bessadóttir M, Eiríksson FF, Becker S, et al. Anti-proliferative and pro-apoptotic effects of lichen-derived compound protolichesterinic acid are not mediated by its lipoxygenase-inhibitory activity. Prostaglandins Leukot Essent Fat Acids. 2015;98:39–47.
   PubMed Web of Science ®Google Scholar
• Watson D, Baharlouei A, Altemimi A, et al. Phytochemicals: extraction, isolation, and identification of bioactive compounds from plant extracts. Plants. 2017;6(4):42.
   Google Scholar
• Dung NTM. Some triterpenoids and steroids from the lichen Lobaria orientalis, lobariaceae. J Sci Technol. 2016;54(2C):313–319.
   Google Scholar
• Brandao LFG, Alcantara GB, Matos MDFC, et al. Cytotoxic evaluation of phenolic compounds from lichens against melanoma cells. Chem Pharm Bull. 2013;61(2):176–183.
   PubMed Web of Science ®Google Scholar
• Bačkorová M, Bačkor M, Mikeš J, et al. Variable responses of different human cancer cells to the lichen compounds parietin, atranorin, usnic acid and gyrophoric acid. Toxicol Vitr. 2011;25(1):37–44.
   PubMed Web of Science ®Google Scholar
• Koparal AT, Ulus G, Zeytinog M, et al. Angiogenesis inhibition by a lichen compound olivetoric acid. Phytother Res. 2010;758:754–758.
   Google Scholar
• Triggiani D, Ceccarelli D, Tiezzi A, et al. Antiproliferative activity of lichen extracts on murine myeloma cells. Biologia. 2009;64(1):59–62.
   Web of Science ®Google Scholar
• Yang Y, Nguyen TT, Jeong M-H, et al. Inhibitory activity of (+)-usnic acid against non-small cell lung cancer cell motility. PLoS One. 2016;11(1):e0146575.
   PubMed Web of Science ®Google Scholar
• Ghate NB, Chaudhuri D, Sarkar R, et al. An antioxidant extract of tropical lichen, Parmotrema reticulatum, induces cell cycle arrest and apoptosis in breast carcinoma cell line MCF-7. PLoS One. 2013;8(12):e82293.
   PubMed Web of Science ®Google Scholar
• Taş İ, Yildirim A, Çobanoğlu G, et al. Determination of biological activities (antibacterial, antiaoxidant and antiproliferative) and metabolite analysis of some lichen species from Turkey. Eur J Biomed Pharm Sci. 2017;4:13–20.
   Google Scholar
• Ranković BR, Kosanić MM, Stanojković TP. Antioxidant, antimicrobial and anticancer activity of the lichens Cladonia furcata, Lecanora atra and Lecanora muralis. BMC Complement Altern Med. 2011;11(97):1–8.
   PubMedGoogle Scholar
• Yu X, Guo Q, Su G, et al. Usnic acid derivatives with cytotoxic and antifungal activities from the lichen Usnea longissima. J Nat Prod. 2016;79(5):1373–1780.
   PubMed Web of Science ®Google Scholar
• Long XH, Zhao K, Zhang GM, et al. Interaction between fatty acid synthase and human epidermal growth receptor 2 (HER2) in osteosarcoma cells. Int J Clin Exp Pathol. 2014;7(12):8777–8783.
   PubMed Web of Science ®Google Scholar
• Cheng C-S, Wang Z, Chen J. Targeting FASN in breast cancer and the discovery of promising inhibitors from natural products derived from traditional Chinese medicine. Evid Based Complement Altern Med. 2014;2014(232946):1–17.
   Google Scholar
• Ebrahim HY, Akl MR, Elsayed HE, et al. Usnic acid benzylidene analogues as potent mechanistic target of rapamycin inhibitors for the control of breast malignancies. J Nat Prod. 2017;80(4):932–952.
   PubMed Web of Science ®Google Scholar
• Mayer M, O’Neill MA, Murray KE, et al. Usnic acid: a non-genotoxic compound with anti-cancer properties. Anticancer Drugs. 2005;16(8):805–809.
   PubMed Web of Science ®Google Scholar
• Ari F, Ulukaya E, Oran S, et al. Promising anticancer activity of a lichen, Parmelia sulcata Taylor, against breast cancer cell lines and genotoxic effect on human lymphocytes. Cytotechnol. 2015;67(3):531–543.
   PubMed Web of Science ®Google Scholar
• Kumar KCS, Müller K. Lichen metabolites. 2. Antiproliferative and cytotoxic activity of gyrophoric, usnic, and diffractaic acid on human keratinocyte growth. J Nat Prod. 1999;62(6):821–823.
   PubMed Web of Science ®Google Scholar
• Brisdelli F, Perilli M, Sellitri D, et al. Cytotoxic activity and antioxidant capacity of purified lichen metabolites: an in vitro study. Phyther Res. 2013;27(3):431–437.
   PubMed Web of Science ®Google Scholar
• Hong JM, Suh SS, Kim TK, et al. Anti-cancer activity of lobaric acid and lobarstin extracted from the antarctic lichen Stereocaulon alpnum. Molecules. 2018;23(658):1–10.
   Google Scholar
• Farkas B, Hantschel M, Magyarlaki M, et al. Heat shock protein 70 membrane expression and melanoma-associated marker phenotype in primary and metastatic melanoma. Melanoma Res. 2003;13(2):147–152.
   PubMed Web of Science ®Google Scholar
• Burlando B, Ranzato E, Volante A, et al. Antiproliferative effects on tumour cells and promotion of keratinocyte wound healing by different lichen compounds. Planta Med. 2009;75(6):607–613.
   PubMed Web of Science ®Google Scholar
• Liu C, Zhang M, Zhang Z, et al. Synthesis and anticancer potential of novel xanthone derivatives with 3,6-substituted chains. Bioorg Med Chem. 2016;24(18):4263–4271.
   PubMed Web of Science ®Google Scholar
• Martins MCB, Rocha TA, Silva TDS, et al. In vitro and in vivo antineoplastic activity of barbatic acid. Int Arch Med. 2016;9(63):1–9.
   Google Scholar
• Stojanovic IZ, Najman S, Jovanovic O, et al. Effects of depsidones from Hypogymnia physodes on hela cell viability and growth. Folia Biol (Praha). 2014;60(2):89–94.
   PubMed Web of Science ®Google Scholar
• Brisdelli F, Perilli M, Sellitri D, et al. Protolichesterinic acid enhances doxorubicin-induced apoptosis in HeLa cells in vitro. Life Sci. 2016;158:89–97.
   PubMed Web of Science ®Google Scholar
• Yang Y, Kyun Bae W, Nam S, et al. Acetone extracts of endolichenic fungus EL002332 isolated from Endocarpon pusillum exhibit anticancer activity against human gastric cancer cells. Phytomed. 2018;40:106–115.
   PubMed Web of Science ®Google Scholar
• Tokiwano T, Satoh H, Obara T, et al. A lichen substance as an antiproliferative compound against HL-60 human leukemia cells: 16-O-acetyl-leucotylic acid isolated from Myelochroa aurulenta. Biosci Biotechnol Biochem. 2009;73(11):2525–2527.
   PubMed Web of Science ®Google Scholar
• Ögmundsdóttir HM, Zoëga GM, Gissurarson SR, et al. Anti-proliferative effects of lichen-derived inhibitors of 5-lipoxygenase on malignant cell-lines and mitogen-stimulated lymphocytes. J Pharm Pharmacol. 1998;50(1):107–115.
   PubMed Web of Science ®Google Scholar
• Nguyen TTH, Dinh MH, Chi HT, et al. Antioxidant and cytotoxic activity of lichens collected from Bidoup Nui Ba National Park, Vietnam. Res Chem Intermed. 2019;45(1):33–49.
   Web of Science ®Google Scholar
• Emsen B, Aslan A, Togar B, et al. In vitro antitumor activities of the lichen compounds olivetoric, physodic and psoromic acid in rat neuron and glioblastoma cells. Pharm Biol. 2016;54(9):1748–1762.
   PubMed Web of Science ®Google Scholar
• Poornima S. Evaluation of anti-cancer properties of lichens using Albino wistar rats as an animal model. Cancer Res J. 2016;4(6):84.-89.
   Google Scholar
• Felczykowska A, Pastuszak-Skrzypczak A, Pawlik A, et al. Antibacterial and anticancer activities of acetone extracts from in vitro cultured lichen-forming fungi. BMC Complement Altern Med. 2017;17(1):300.
   PubMedGoogle Scholar
• Mishra T, Shukla S, Meena S, et al. Isolation and identification of cytotoxic compounds from a fruticose lichen Roccella montagnei, and it’s in silico docking study against CDK-10. Braz J Pharmacogn. 2017;27(6):724–728.
   Google Scholar
• Robelo TK, Zeidan GF, Vasques LM, et al. Redox characterization of usnic acid andits cytotoxic effect on human neuron-like cells (SH-SY5Y). Toxicol In Vitr. 2012;26(2):304–314.
   PubMed Web of Science ®Google Scholar
• Liu H, Liu YQ, Liu YQ, et al. A novel anticancer agent, retigeric acid B, displays proliferation inhibition, S phase arrest and apoptosis activation in human prostate cancer cells. Chem Biol Interact. 2010;188(3):598–606.
   PubMed Web of Science ®Google Scholar