Types A and D Trichothecene Mycotoxins from the Fungus Myrothecium roridum

Waranya Lakornwong; Kwanjai Kanokmedhakul; Kasem Soytong; Arm Unartngam; Sarawut Tontapha; Vittaya Amornkitbamrung; Somdej Kanokmedhakul

doi:10.1055/a-0895-5753

Planta Medica, Inhaltsverzeichnis

Planta Med 2019; 85(09/10): 774-780
DOI: 10.1055/a-0895-5753

Natural Product Chemistry and Analytical Studies

Original Papers

Georg Thieme Verlag KG Stuttgart · New York

Types A and D Trichothecene Mycotoxins from the Fungus Myrothecium roridum

Waranya Lakornwong

¹Natural Products Research Unit, Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand

,

Kwanjai Kanokmedhakul

¹Natural Products Research Unit, Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand

,

Kasem Soytong

²Department of Plant Production Technology, Faculty of Agricultural Technology, King Mongkutʼs Institute of Technology Ladkrabang, Bangkok, Thailand

,

Arm Unartngam

³Bioproduct Science, Department of Science, Faculty of Liberal Arts and Science, Kasetsart University Kamphaeng Saen Campus, Nakorn Pathom, Thailand

,

Sarawut Tontapha

⁴Integrated Nanotechnology Research Center, Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand

,

Vittaya Amornkitbamrung

⁴Integrated Nanotechnology Research Center, Department of Physics, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand

,

Somdej Kanokmedhakul

¹Natural Products Research Unit, Department of Chemistry and Center of Excellence for Innovation in Chemistry, Faculty of Science, Khon Kaen University, Khon Kaen, Thailand

› Institutsangaben

Abstract

Chromatographic separation of extracts from the fungal biomass of a plant pathogenic fungus, Myrothecium roridum, yielded 8 trichothecene toxins including 6 type D trichothecenes (1–6) and 2 type A trichothecenes (7–8). 6′,12′-Epoxymyrotoxin A (1) and 7′-hydroxymytoxin B (2) were new macrocyclic trichothecenes, while the other trichothecenes were identified as myrotoxin B (3), myrotoxin D hydrate (4), 2′,3′-epoxymyrothecine A (5), miotoxin A (6), and 2 trichothecenes lacking the macrocyclic lactone system, roridin L-2 (7) and trichoverritone (8). The structures of these mycotoxins were characterized using spectroscopic methods. The absolute configurations of 1 and 2 were determined by NOESY and a comparison of their experimental and calculated ECD spectra. Most of these mycotoxins (1–4 and 6) exhibited highly potent antimalarial activity against Plasmodium falciparum. They also showed strong cytotoxicity towards KB and NCI-H187 cell lines (IC₅₀ 0.60 – 112.28 nM), as well as the Vero cell line (IC₅₀ 1.50 – 46.51 nM).

Key words

Myrothecium roridum - endophyte - trichothecenes - antimalarial activity - cytotoxicity - mycotoxin - Tuberculariaceae

Volltext

Referenzen

References
1 Domsch KH, Gams W, Anderson TH. Compendium of Soil Fungi. London: Academic Press; 1980: 483-484
2 Fish WW, Bruton BD, Popham TW. Cucurbit host range of Myrothecium roridum isolated from watermelon. Am J Plant Sci 2012; 3: 353-359
3 Chase AR. Influence of host plant and isolate source on Myrothecium leaf spot of foliage plants. Plant Dis 1983; 67: 668-671
4 Ponnappa KM. On the pathogenicity of Myrothecium roridum–Eichhornia crassipes isolate. Hyacinth Control Jnl 1970; 8: 18-20
5 Cabral CS, Henz GP, Moreira AJA, Reis A. New cucurbitaceous hosts of Myrothecium roridum in Amazonas State, Brazil. Trop Plant Pathol 2009; 34: 402-405
6 Quezado-Duval AM, Henz GP, Paz-Lima ML, Medeiros AR, Miranda BEC, Pfenning LH, Reis A. New hosts of Myrothecium spp. in Brazil and a preliminary in vitro assay of fungicides. Braz J Microbiol Publ Braz Soc Microbiol 2010; 41: 246-252
7 Hong CF, Tsai SF, Yeh HC, Fan MC. First report of Myrothecium roridum causing Myrothecium leaf spot on Dieffenbachia picta “Camilla” in Taiwan. Plant Dis 2013; 97: 1253
8 Bloem RJ, Smitka TA, Bunge RH, French JC, Mazzola EP. Roridin-L-2, a new trichothecene. Tetrahedron Lett 1983; 24: 249-252
9 Jarvis BB, Vrudhula VM, Pavanasasivam G. Trichoverritone and 16-hydroxyroridin L-2, new trichothecenes from Myrothecium roridum . Tetrahedron Lett 1983; 24: 3539-3542
10 Lin T, Wang G, Zhou Y, Zeng D, Liu X, Ding R, Jiang X, Zhu D, Shan W, Chen H. Structure elucidation and biological activity of two new trichothecenes from an endophyte, Myrothecium roridum . J Agric Food Chem 2014; 62: 5993-6000
11 Wang T, Zhang Y, Pei Y. Two novel trichothecenes from Myrothecium roridum . Med Chem Res 2007; 16: 155-161
12 De Carvalho MP, Weich H, Abrahum WR. Macrocyclic trichothecenes as antifungal and anticancer compounds. Curr Med Chem 2016; 23: 23-35
13 He J, Zhou T, Young JC, Boland GJ, Scott PM. Chemical and biological transformations for detoxification of trichothecene mycotoxins in human and animal food chains: a review. Trends Food Sci Technol 2010; 21: 67-76
14 Rizzo I, Varsavky E, Haidukowski M, Frade H. Macrocyclic trichothecenes in Baccharis coridifolia plants and endophytes and Baccharis artemisioides plants. Toxicon 1997; 35: 753-757
15 McCormick SP, Stanley AM, Stover NA, Alexander NJ. Trichothecenes: from simple to complex mycotoxins. Toxins (Basel) 2011; 3: 802-814
16 Islam Z, Shinozuka J, Harkema JR, Pestka JJ. Purification and comparative neurotoxicity of the trichothecenes satratoxin G and roridin L2 from Stachybotrys chartarum . J Toxicol Environ Health A 2009; 72: 1242-1251
17 Zhang HJ, Tamez PA, Aydogmus Z, Tan GT, Saikawa Y, Hashimoto K, Nakata M, Hung NV, Xuan le T, Cuong NM, Soejarto DD, Pezzuto JM, Fong HH. Antimalarial agents from plants. III. Trichothecenes from Ficus fistulosa and Rhaphidophora decursiva . Planta Med 2002; 68: 1088-1091
18 Rocha O, Ansari K, Doohan FM. Effects of trichothecene mycotoxins on eukaryotic cells: a review. Food Addit Contam 2005; 22: 369-378
19 Pestka JJ, Smolinski AT. Deoxynivalenol: toxicology and potential effects on humans. J Toxicol Environ Health B Crit Rev 2005; 8: 39-69
20 Jarvis BB, Lee YW, Cömezoḡlu FT, Cömezoḡlu SN, Bean GA. Myrotoxins: a new class of macrocyclic trichothecenes. Tetrahedron Lett 1985; 26: 4859-4862
21 Jarvis BB, Comezoglu FT, Wang S, Ammon HL. Myrotoxins from a plant pathogenic isolate of Myrothecium roridum . Mycotoxin Res 1991; 7: 73-78
22 Habermehl GG, Stegemann J. Miotoxin-A: a novel macrocyclic trichothecene from the Brazilian plant Baccharis coridifolia . Z Naturforsch C 2014; 39: 212-216
23 Jarvis BB, Kollah RO, Zeng M. Chemical modification of the macrocyclic trichothecenes, maccharinoid B4 and myrotoxin B. Quim Nova 1990; 13: 315-326
24 McPhail AT, Sim GA. Fungal metabolites. Part VI. The structure of verrucarin A: X-ray analysis of verrucarin A p-iodobenzenesulphonate. J Chem Soc Perkin 1 1966; 16: 1394-1406
25 Jarvis BB, Çömezoglu FT, Lee YW, Flippen-Anderson JL, Gilardi RD, George CF. Novel macrocyclic trichothecenes from Myrothecium roridum . Bull Soc Chim Belg 1986; 95: 681-697
26 Frisch MJ, Trucks GW, Schlegel HB, Scuseria GE, Robb MA, Cheeseman JR, Scalmani G, Barone V, Mennucci B, Petersson GA, Nakatsuji H, Caricato M, Li X, Hratchian HP, Izmaylov AF, Bloino J, Zheng G, Sonnenberg JL, Hada M, Ehara M, Toyota K, Fukuda R, Hasegawa J, Ishida M, Nakajima T, Honda Y, Kitao O, Nakai H, Vreven T, Montgomery jr. JA, Peralta JE, Ogliaro F, Bearpark M, Heyd JJ, Brothers E, Kudin KN, Staroverov VN, Kobayashi R, Normand J, Raghavachari K, Rendell A, Burant JC, Iyengar SS, Tomasi J, Cossi M, Rega N, Millam JM, Klene M, Knox JE, Cross JB, Bakken V, Adamo C, Jaramillo J, Gomperts R, Stratmann RE, Yazyev O, Austin AJ, Cammi R, Pomelli C, Ochterski JW, Martin RL, Morokuma K, Zakrzewski VG, Voth GA, Salvador P, Dannenberg JJ, Dapprich S, Daniels AD, Farkas Ö, Foresman JB, Ortiz JV, Cioslowski J, Fox DJ. Gaussian09, revision B. 01. Wallingford: Gaussian Inc.; 2010
27 Parr RG, Young W. Density functional Theory of Atoms and Molecules. London: Oxford University Press; 1989: 5-15
28 Yanai T, Tew DP, Handy NC. A new hybrid exchange-correlation functional using the Coulomb-attenuating method (CAM-B3LYP). Chem Phys Lett 2004; 393: 51-57
29 Cossi M, Barone V. Time-dependent density functional theory for molecules in liquid solutions. J Chem Phys 2001; 115: 4708-4717
30 Piyaboon O. Biological control of water hyacinth using Myrothecium roridum isolated from Thailand [Dissertation]. Bangkok: Kasetsart University; 2016
31 Thaithong S, Beale GH. Resistance of ten Thai isolates of Plasmodium falciparum to chloroquine and pyrimethamine by in vitro tests. Trans R Soc Trop Med Hyg 1981; 75: 271-273
32 Trager W, Jensen JB. Human malaria parasites in continuous culture. Science 1976; 193: 673-675
33 Desjardins RE, Canfield CJ, Haynes JD, Chulay JD. Quantitative assessment of antimalarial activity in vitro by a semiautomated microdilution technique. Antimicrob Agents Chemother 1979; 16: 710-718
34 OʼBrien J, Wilson I, Orton T, Pognan F. Investigation of the Alamar Blue (resazurin) fluorescent dye for the assessment of mammalian cell cytotoxicity. Eur J Biochem 2000; 267: 5421-5426
35 Hunt L, Jordan M, De Jesus M, Wurm FM. GFP-expressing mammalian cells for fast, sensitive, noninvasive cell growth assessment in a kinetic mode. Biotechnol Bioeng 1999; 65: 201-205

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