Cytotoxic and Antiviral Compounds from Bryophytes and Inedible Fungi
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Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, Japan
Department of Pharmacognosy with Medicinal Plants Laboratory, Medical University of Lublin, Poland
Yoshinori Asakawa   

Faculty of Pharmaceutical Sciences, Tokushima Bunri University, Yamashiro-cho, Tokushima, Japan
J Pre Clin Clin Res. 2013;7(2):73–85
Over several hundred new compounds have been isolated from the bryophytes and more than 40 new carbon skeletal terpenoids and aromatic compounds found in this class. Most of liverworts elaborate characteristic odiferous, pungent and bitter tasting compounds many of which show, antimicrobial, antifungal, antiviral, allergenic contact dermatitis, cytotoxic, insecticidal, anti-HIV, superoxide anion radical release, plant growth regulatory, neurotrophic, NO production inhibitory, muscle relaxing, antiobesity, piscicidal and nematocidal activity. Several inedible mushrooms produce spider female pheromones, strong antioxidant, or cytotoxic compounds. The present paper concerns with the isolation of terpenoids, aromatic compounds and acetogenins from several bryophytes and inedible fungi and their cytotoxic and antiviral activity.
Asakawa Y, Huneck S, Toyota M, Takemoto T, Suire C. Mono- and sesquiterpenes from Porella arboris-vitae. J Hatt Bot Lab. 1979; 46: 163–167.
Asakawa Y. Chemical constituents of the Hepaticae. In: Herz W, Grisebach H, Kirby G.W, eds. Progress in the chemistry of organic natural products. Vienna, Springer, 1982. 42, p.1–285.
Asakawa Y. Chemical constituents of the bryophytes. In: Herz W, Kirby WB, Moore RE, Steglich W, Tamm Ch. eds. Progress in the chemistry of organic natural products. Vienna, Springer, 1995.p.1- 618.
Asakawa Y, Ludwiczuk A, Nagashima F. Chemical constituents of bryophytes: Bio- and chemical diversity, biological activity and chemosystematics. In: Kinghorn DA, Falk H, Kobayashi J. eds. Progress in the chemistry of organic natural products. Springer, Vienna, 2013.p. 1–796.
Ludwiczuk A, Asakawa Y. Distribution of terpenoids and aromatic compounds in selected southern hemispheric liverworts. Fieldiana Bot. 2008; 47: 37–58.
Ludwiczuk A, Asakawa Y. Chemosystematics of the liverworts collected in Borneo. Tropic Bryol. 2010; 31: 33–42.
Ludwiczuk A, Nagashima F, Gradstein SR, Asakawa Y. Volatile Components from the selected Mexican, Ecuadorian, Greek, German and Japanese liverworts. Nat Prod Commun. 2008; 3: 133–140.
Ludwiczuk A, Komala I, Pham A, Bianchini JP, Raharivelomanana P, Asakawa Y. Volatile components from selected Tahitian liverworts. Nat. Prod. Commun. 2009; 4: 1387–1392.
Asakawa Y. Phytochemistry of bryophytes: biologically active terpenoids and aromatic compounds from liverworts. In: Romeo J. ed. Phytochemicals in human health protection, nutrition, and plant defense. New York, Kluwer Academic/Plenum Publishers, 1999.p.319– 342.
Asakawa Y. Liverworts – potential source of medicinal compounds. Curr Pharm Design. 2008; 14: 3067–3088.
Asakawa Y. Recent advances of biologically active substances from Marchantiophyta. Nat Prod Commun. 2008; 3: 77–92.
Asakawa Y. Biologically active substances from bryophytes. In: Chopra RN, Bhatla SC. eds. Bryophyte development: Physiology and biochemistry. Boca Raton, CRC Press, 1990.p.259–287.
Asakawa Y. Terpenoids and aromatic compounds with pharmacological activity from bryophytes. In: Zinsmeister DH, Mues R, eds. Bryophytes: Their chemistry and chemical taxonomy. Oxford, Oxford University Press, 1990.p.369–410.
Mohamed H, Baki BB, Nasrulhaq-Boyce A, Lee PK Y. eds. In: Bryology in the new millenium. Kuala Lumpur, University of Malaya, 2008.p.1–513.
Inoue H. Bryophytes as a indicator of continental drift (Gondwana land). Kagakuasahi 1988; 8: 116–121.
von Reuβ SH, Konig WA. Corsifurans A-C, 2-arylbenzofurans of presumed stilbenoid origin from Corsinia coriandrina (Hepaticae). Phytochemistry 2004; 65: 3113–3118.
Toyota M, Tanimura K, Asakawa Y. Cytotoxic 2,3-Secoaromadendranetype sesquiterpenoids from the liverwort Plagiochila ovalifolia. Planta Med. 1998; 64: 462–464.
Shu YF, Wei HC, Wu CL. Sesquiterpenoids from liverworts Lepidozia vitrea and L. fauriana. Phytochemistry 1994; 37: 773–776.
Lu, Z. -Q., Fan, P. -H., Ji, M., Lou, H. -X. Terpenoids and bisbibenzyls from Chinese liverworts Conocephalum conicum and Dumortiera hirsuta. J. Asian Nat. Prod. Res. 2006; 8: 187–192.
Komala I. Ito T, Nagashima F, Yagi Y, Asakawa Y, Cytotoxic, radical scavenging and antimicrobial activities of sesquiterpenoids from the Tahitian liverwort Mastigophora diclados (Brid.) Nees (Mastigophoraceae). J Nat Med. 2010; 64: 417–422.
Wang Y, Harrison LJ, Tan BC. Terpenoids from the liverwort Chandonanthus hirtellus. Tetrahedron 2009; 65: 4035–4043.
Komala I, Ito T, Nagashima F, Yagi Y, Asakawa Y. New sesqui- and diterpenoids from the liverwort Chandonanthus hirtellus. The 53rd Symposium on Chemistry of Terpenes, Essential Oils and Aromatics; November 7–9, 2009; Nara, Japan. Symposium Papers, p.266–268.
Wu C, Gunatilaka AAL, McCabe FL, Johnson RK, Spjut RW, Kingston DG.I. Bioactive and other sesquiterpenes from Chiloscyphus rivularis. J Nat Prod. 1997; 60: 1281–1286.
Baek SH, Perry NB, Lorimer SD, ent-Costunolide from the liverwort Hepatostolonophora paucistipula. J. Chem. Research (S). 2003; 14–15.
Kim, Y. C., da S. Bolzani, V., Baj, N., Gunatilaka, A. A. L., Kingston, D. G. I. A DNA-damaging sesquiterpene and other constituents from Frullania nisquallensis. Planta Med. 1996; 62: 61–63.
Burgess EJ, Larsen L, Perry NB. A Cytotoxic sesquiterpene caffeate from the liverwort Bazzania novae-zelandiae. J Nat Prod. 2000; 63: 537–539.
Perry NB, Foster LM. Sesquiterpene/quinol from a New Zealand liverwort, Riccardia crassa. J Nat Prod. 1995; 58: 1131–1135.
Komala I, Ito T, Nagashima F, Yagi Y, Kawahata M, Yamaguchi K, et al. Zierane sesquiterpene lactone, cembrane and fusicoccane diterpenoids, from the Tahitian liverwort Chandonanthus hirtellus. Phytochemistry 2010; 71: 1387–1394.
Scher JM, Burgess EJ, Lorimer SD, Perry NB. A cytotoxic sesquiterpene and unprecedented sesquiterpene-bisbibenzyl compounds from the liverwort Schistochila glaucescens. Tetrahedron 2002; 58: 7875–7882.
Lorimer, S. D., Perry, N. B., Burgess, E. J., Foster, L. M. 1-Hydroxyditerpenes from two New Zealand liverworts, Paraschistochila pinnatifolia and Trichocolea mollissima. J Nat Prod. 1997; 60: 421–424.
Perry NB, Burgess E J, Tangney RS. Cytotoxic 8,9-secokaurane diterpenes from a New Zealand Liverwort, Lepidolaena taylorii. Tetrahedron Lett. 1996; 37: 9387–9390.
Perry NB, Burgess EJ, Baek SH, Weavers RT, Geis W, Mauger AB. 1999. 11-Oxygenated cytotoxic 8,9-secokauranes from a New Zealand liverwort, Lepidolaena taylorii. Phytochemistry 1999; 50: 423–433.
Nagashima F., Kondoh M, Uematsu T, Nishiyama A, Saito S, Sato M, et al. Cytotoxic and apoptosis-Inducing ent-kaurane-type diterpenoids from the Japanese liverwort Jungermannia trunctata Nees. Chem Pharm Bull. 2002; 50: 808–813.
Perry NB, Burgess EJ, Foster LM, Gerard PJ, Toyota M, Asakawa Y., 2008. Insect antifeedant sesquiterpene acetals from the liverwort Lepidolaena clavigera. 2. Structures, artifacts and activity. J Nat Prod. 1998; 71: 258–261.
Perry NB, Burgess EJ, Baek SH, Weavers RT. The First atisane diterpenoids from a liverwort: Polyols from Lepidolaena clavigera. Org Lett. 2001; 3: 4243–4245.
Neves M, Morais R, Gafner S, Hostettmann K. Three triterpenoids and one flavonoid from the liverwort Asterella blumeana grown in vitro. Phytotherapy Res. 1998; 12: 21–24.
Wong SM, Oshima Y, Pezzuto J, Fong H, Farnsworth N. Plant anticancer agents XXXIX. Triterpenes from Isis missouriensis (Iridaceae). J Pharm Sci. 1986; 75: 317–320.
Komala I, Ito T, Nagashima F, Yagi Y, Asakawa Y. Cytotoxic bibenzyls, germacrane- and pinguisane-type sesquiterpenoids from the Indonesian, Tahitian and Japanese liverworts. Nat Prod Commun. 2011; 6: 303–309.
Asakawa Y, Toyota M, Tori M, Hashimoto T. Chemical structures of macrocyclic bis(bibenzyls) isolated from liverworts (Hepaticae). Spectroscopy 2000; 14: 149–175.
Asakawa Y, Matsuda R. Riccardin C, a novel cyclic bibenzyl derivative from Reboulia hemisphaerica. Phytochemistry 1982; 21: 2143–2144.
Huang WJ, Wu CL, Lin CW, Chi LL, Chen PY, Chiu CJ, et al. Marchantin A, a cyclic bis(bibenzyl ether), isolated from the liverwort Marchantia emarginata subsp. tosana induces apoptosis in human MCF-7 breast cancer cells. Cancer Lett. 2010; 291: 108–119.
Xie CF, Qu JB, Wu XZ, Liu N, Ji M, Lou HX. Antifungal macrocyclic bis(bibenzyls) from the Chinese liverwort Plagiochasma intermedium L. Nat Prod. Res. 2010; 24; 515–520.
Shi YQ, Liao YX, Qu XJ, Yuan HQ, Li S, Qu JB, et al. Marchantin C, a macrocyclic bisbibenzyl, induces apoptosis of human glioma A172 cells. Cancer Lett. 2008; 262: 173–182.
Shi YQ, Qu XJ, Liao YX, Xie CF, Cheng YN, Li S. et al. Reversal effect of a macrocyclic bisbibenzyl plagiochin E on multidrug resistance in adriamycin-resistant K562/A02 cells. Eur. J. Pharmacol. 2008; 584: 66–71.
Speicher A, Groh M, Zapp J, Schaumloffel A, Knauer M, Bringmann G.. Synthesis-driven structure revision of ‘plagiochin E’, a highly bioactive bisbibenzyl. Synlett. 2009; 1852–1858.
Lorimer SD, Perry NB. Antifungal hydroxyacetophenones from the New Zealand liverwort, Plagiochila fasciculata. Planta Med. 1994; 60: 386–387.
Perry NB, Foster LM, Lorimer SD, May BCH, Weavers RT, Toyota M, et al. Isoprenyl phenyl ethers from liverworts of the genus Trichocolea: Cytotoxic activity, structural corrections, and synthesis. J Nat Prod. 1996; 59: 729–733.
Baek SH, Oh HJ, Lim JA, Chun HJ, Lee HO, Ahn JW, et al. Biological activities of Methyl-4-[[(2E)-3,7-dimethyl-2,6-octadienyl]oxy]-3- hydroxybenzoate. Bull. Korean Chem Soc. 2004; 25: 195–197.
Nagashima F, Kasai W, Kondoh M, Fujii M. Watanabe Y, Braggins J. E, et al. New ent-kaurene-type diterpenoids possessing cytotoxicity from the New Zealand liverwort Jungermannia species. Chem Pharm Bull. 2003; 51: 1189–1192.
Nagashima F, Kondoh M, Fujii M, Takaoka S, Watanabe Y, Asakawa Y. Novel cytotoxic diterpenoids from the New Zealand liverwort Jungermannia species. Tetrahedron 2005; 51: 4531–4544.
Nagashima F, Kondoh M, Kawase M, Simizu S, Osada H, Fuji M, et al. Apoptosis-inducing properties of ent-kaurene-type diterpenoids from the liverwort Jungermannia trunctata. Planta Med. 2003; 69: 377–379.
Kondoh M, Suzuki I, Sato M, Nagashima F, Simizu S, Harada al. 2004. Kaurene diterpene induces apoptosis in human leukemia cells partly through a caspase-8-dependent pathway. J Pharmacol Exp Ther. 2004; 311: 115–122.
Suzuki I, Kondoh M, Harada M, Koizumi N, Fujii M, Nagashima F, et al. An ent-kaurene diterpene enhances apoptosis induced by tumor necrosis factor in human leukemia cells. Planta Med. 2004; 70: 723–727.
Suzuki I, Kondoh M, Nagashima F, Fujii M, Asakawa Y, Watanabe Y. A comparison of apoptosis and necrosis induced by ent-kaurene-type diterpenoids in HL-60 cells. Planta Med. 2004; 70: 401–406.
Kondoh M, Nagashima F, Suzuki I, Harada M, Fuji M, Asakawa Y, et al. Induction of apoptosis by new ent-kaurene-type diterpenoids isolated from the New Zealand liverwort Jungermannia species. Planta Med. 2005; 71: 1005–1009.
Kondoh M, Suzuki I, Harada M, Nagashima F, Fuji M, Asakawa Y. et al. Activation of p38 mitogen-activated protein kinase during ent- 11α-hydroxy-16-kauren-15-one-induced apoptosis in human leukemia HL-60 cells. Planta Med. 2005; 71: 275–277.
Izumi S, Nishio Y, Takashima O, Hirata T. Monoterpenoids, potent inducers of apoptosis in the cells of Marchantia polymorpha. Chem Lett. 1997; 837–838.
Guo DX, Du Y, Wang YY, Sun LM, Qu JB, Wang XN, et al. Secondary metabolites from the liverwort Ptilidium pulcherrimum. Nat Prod Commun. 2009; 4: 1319–1322.
Nozaki H, Hayashi KI, Nishimura N, Kawaide H, Matsuo A, Takaoka D. 2007. Momilactone A and B as allelochemicals from moss Hypnum plumaeforme: First occurrence in bryophytes. Biosci Biotechnol Biochem 2007; 71: 3127–3130.
Kim SJ, Park HR, Park E, Lee SC. Cytotoxic and antitumor activity of momilactone B from rice hulls. J Agric Food Chem. 2007; 55: 1702–1706.
Zheng G.Q, Ho DK, Elder PJ, Stephens RE, Cottrell CE, Cassady JM. Ohioensins and pallidisetins: Novel cytotoxic agents from the moss Polytrichum pallidisetum. J Nat Prod. 1994; 57: 32–41.
Fu P, Lin S, Shan L, Shen, YH, Tang J, Liu RH, et al. Constituents of the moss Polytrichum commune. J Nat Prod. 2009; 72: 1335–1337.
Asakawa Y, Ludwiczuk, A. Distribution of cyclic bis-bibenzyls in the Marchantiophyta (liverworts), ferns and higher plants and their biological activities, biosynthesis, and total synthesis. Heterocycles. 2012; 86: 891–917.
Iwai Y, Murakami K, Gomi Y, Hashimoto T, Asakawa Y, Okuno Y, et al. Anti-influenza activity of marchantins, macrocyclic bisbibenzyls contained in liverworts. PLoS ONE. 2011; 6: 19825.
Yoshida T, Hashimoto T, Takaoka S, Kan Y, Tori M, Asakawa Y. Phenolic constituents of the liverwort: Four novel cyclic Bisbibenzyl dimers from Blasia pusilla L. Tetrahedron 1996; 52: 14487–14500.
Shi YQ, Zhu CJ, Yuan HQ, Li BQ, Gao J, Qu XJ, et al. Marchantin C, a novel microtubule inhibitor from liverwort with anti-tumor activity both in vivo and in vitro. Cancer Lett. 2009; 276: 160–170.
Morita H, Tomizawa Y, Tsuchiya T, Hirasawa Y, Hashimoto T, Asakawa Y. Antimitotic activity of two macrocyclic bis(bibenzyls), isoplagiochins A and B from the liverwort Plagiochila fruticosa. Bioorg Med Chem Lett. 2009; 19: 493–496.
Hashimoto T, Yasuda A, Akazawa K, Takaoka S, Tori M, Asakawa Y. Three novel dimethyl pyrroledicarboxylate, lycogarubin A-C, from the Myxomycetes Lycogala epidendrum. Tetrahedron Lett. 1994; 35: 2559–2560.
Quang DN, Hashimoto T, Asakawa Y. Inedible mushrooms, a good source of biologically active compounds. J Chem Rec. 2006; 6: 79–99.
Asakawa Y, Hashimoto T, Mizuno Y, Tori M. Cryptoporic acids A-G, drimane-type sesquiterpenoid ethers of isocitoric acid from the fungus Cryptoporus volvatus. Phytochemistry 1992; 31: 579–592.
Buchanan MS, Hashimoto T, Asakawa Y. Cytochalasins from a Daldinia sp. of fungus. Phytochemistry 1996; 41: 821–828.
Kashiwada Y, Yamazaki K, Ikeshiro Y, Yamagishi T, Fujioka T, Mihashi K, et al. 2001. Isolation of rhododaurichromanic acid B and the anti- HIV principles rhododaurichromanic acid A and rhododaurichromenic acid from Rhododendron dauricum. Tetrahedron. 2001; 57:1559–15.