Planta Med 2010; 76(10): 1004-1006
DOI: 10.1055/s-0029-1240897
Natural Product Chemistry
Letters
© Georg Thieme Verlag KG Stuttgart · New York

A New Cytotoxic Trichothecene Macrolide from the Endophyte Myrothecium roridum

Li Shen1 , Jian Shou Wang1 , Hai Jun Shen1 , Yong Chun Song2 , Ren Xiang Tan2
  • 1Medical College, Yangzhou University, Yangzhou, P. R. China
  • 2Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, P. R. China
Further Information

Publication History

received October 13, 2009 revised January 21, 2010

accepted January 25, 2010

Publication Date:
01 March 2010 (online)

Abstract

A new cytotoxic roridin-type trichothecene macrolide named roritoxin E (1) was characterized from the solid culture of Myrothecium roridum IFB-E091 (residing originally inside Artemisia annua root), together with the known compounds lumichrome (2), (22E,24S)-cerevisterol (3), and (22E,24R)-6β-methoxy-ergosta-7,22-diene-3β,5α-diol (4). The structure of the new macrolide (1) was elucidated by a combination of spectroscopic (UV, IR, MS, and 1D and 2D NMR) analyses. Compound 1 was demonstrated to be inhibitory in vitro against the gastric carcinoma SGC-7901 and hepatocarcinoma SMMC-7721 cell lines, with IC50 values of 0.26 and 10.54 µg/mL, respectively. 5-Fluorouracil co-assayed as a positive control had an IC50 value of 6.66 µg/mL against SGC-7901 cells, and it demonstrated only a 9.98 % growth inhibition against SMMC-7721 cells at 10 µg/mL.

References

  • 1 Amagata T, Rath C, Rigot J F, Tarlov N, Tenney K, Valeriote F A, Crews P. Structures and cytotoxic properties of trichoverroids and their macrolide analogues produced by saltwater culture of Myrothecium verrucaria.  J Med Chem. 2003;  46 4342-4350
  • 2 Shen L, Jiao R H, Ye Y H, Wang X T, Xu C, Song Y C, Zhu H L, Tan R X. Absolute configuration of new cytotoxic and other bioactive trichothecene macrolides.  Chem Eur J. 2006;  12 5596-5602
  • 3 Alvi K A, Rabenstein J, Woodard J, Baker D D, Bergthold J D, Lynch J, Lieu K L, Braude I A. 14′-Hydroxymytoxin B and 16-hydroxyroridin E, two new cytotoxic trichothecenes from Myrothecium roridum.  J Nat Prod. 2002;  65 742-744
  • 4 Wagenaar M M, Clardy J. Two new roridins isolated from Myrothecium sp.  J Antibiot. 2001;  54 517-520
  • 5 Jarvis B B, Comezoglu F T, Lee Y-W, Flippen-Anderson J L, Gilardi R D, George C F. Novel macrocyclic trichothecenes from Myrothecium roridum.  Bull Soc Chim Belg. 1986;  95 681-697
  • 6 Sugawara T, Tanaka A, Nagai K, Suzuki K, Okada G. New members of the trichothecene family.  J Antibiot. 1997;  50 778-780
  • 7 Isaka M, Punya J, Lertwerawat Y, Tanticharoen M, Thebtaranonth Y. Antimalarial activity of macrocyclic trichothecenes isolated from the fungus Myrothecium verrucaria.  J Nat Prod. 1999;  62 329-331
  • 8 Pestka J J, Zhou H R, Moon Y, Chung Y J. Cellular and molecular mechanisms for immune modulation by deoxynivalenol and other trichothecenes: unraveling a paradox.  Toxicol Lett. 2004;  153 61-73
  • 9 Abbas H K, Johnson B B, Shier W T, Tak H, Jarvis B B, Boyette C D. Phytotoxicity and mammalian cytotoxicity of macrocyclic trichothecene mycotoxins from Myrothecium verrucaria.  Phytochemistry. 2002;  59 309-313
  • 10 Jarvis B B, Wang S J. Stereochemistry of the roridins. Diastereomers of roridin E.  J Nat Prod. 1999;  62 1284-1289
  • 11 Ge H M, Jiao R H, Zhang Y F, Zhang J, Wang Y R, Tan R X. Cytotoxicity and phytotoxicity of trichothecene macrolides from Myrothecium gramminum.  Planta Med. 2009;  75 227-229
  • 12 Trapp S C, Hohn T M, McCormick S, Jarvis B B. Characterization of the gene cluster for biosynthesis of macrocyclic trichothecenes in Myrothecium roridum.  Mol Gen Genet. 1998;  257 421-432
  • 13 Grove J F. Phytotoxic compounds produced by Fusarium equiseti. Part 8. Acid catalysed rearrangement of 12,13-epoxytrichothec-9-enes.  J Chem Soc [Perkin I]. 1986;  647-654
  • 14 Tokai T, Koshino H, Kawasaki T, Igawa T, Suzuki Y, Sato M, Fujimura M, Eizuka T, Watanabe H, Kitahara T, Ohta K, Shibata T, Kudo T, Inoue H, Yamaguchi I, Kimura M. Screening of putative oxygenase genes in the Fusarium graminearum genome sequence database for their role in trichothecene biosynthesis.  FEMS Microbiol Lett. 2005;  251 193-201
  • 15 Esmond R, Fraser-Reid B, Jarvis B B. Synthesis of trichoverrin B and its conversion to verrucarin J.  J Org Chem. 1982;  47 3358-3360
  • 16 Jeker N, Tamm C. Synthesis of new unnatural macrocyclic trichothecenes: 4-epiverrucarin A. 47th Communication on verrucarins and roridins.  Helv Chim Acta. 2004;  71 1904-1913
  • 17 Grande H J, Van Schagen C G, Jarbandhan T, Muller F. An 1H-NMR spectroscopic study of alloxazines and isoalloxazines.  Helv Chim Acta. 1977;  60 348-366
  • 18 Piccialli V, Sica D. Four new trihydroxylated sterols from the sponge Spongionella gracilis.  J Nat Prod. 1987;  50 915-920
  • 19 Kawagishi H, Katsumi R, Sazawa T, Mizuno T, Hagiwara T, Nakamura T. Cytotoxic steroids from the mushroom Agaricus blazei.  Phytochemistry. 1988;  27 2777-2779
  • 20 Savard M E, Blackwell B A, Greenhalgh R. An 1H nuclear magnetic resonance study of derivatives of 3-hydroxy-12,13-epoxytrichothec-9-enes.  Can J Chem. 1987;  65 2254-2262
  • 21 Grove J F. Macrocyclic trichothecenes.  Nat Prod Rep. 1993;  10 429-448
  • 22 Minato H, Katayama T, Tori K. Vertisporin, a new antibiotic from Verticimonosporium diffractum.  Tetrahedron Lett. 1975;  16 2579-2582
  • 23 Jarvis B B, Yatawara C S. Roritoxins, new macrocyclic triohothecenes from Myrothecium roridum.  J Org Chem. 1986;  51 2906-2910
  • 24 Liu J Y, Huang L L, Ye Y H, Zou W X, Guo Z J, Tan R X. Antifungal and new metabolites of Myrothecium sp. Z16, a fungus associated with white croaker Argyrosomus argentatus.  J Appl Microbiol. 2006;  100 195-202
  • 25 Nielsen C, Casteel M, Didier A, Dietrich R, Martlbauer E. Trichothecene-induced cytotoxicity on human cell lines.  Mycotox Res. 2009;  25 77-84
  • 26 Lu H, Zou W X, Meng J C, Hu J, Tan R X. New bioactive metabolites produced by Colletotrichum sp., an endophytic fungus in Artemisia annua.  Plant Sci. 2000;  151 67-73
  • 27 Larena I, Salazar O, Gonzalez V, Julian M C, Rubio V. Design of a primer for ribosomal DNA internal transcribed spacer with enhanced specificity for ascomycetes.  J Biotechnol. 1999;  75 187-194
  • 28 White T J, Bruns T, Lee S, Taylor J. Amplification and direct sequencing of fungal ribosomal RNA genes for phylogenetics. Innis MA, Gelfand DH, Sninsky JJ, White TJ PCR protocols: a guide to methods and applications. San Diego; Academic Press 1990: 315-322
  • 29 Shen L, Ye Y H, Wang X T, Zhu H L, Xu C, Song Y C, Li H, Tan R X. Structure and total synthesis of aspernigerin: a novel cytotoxic endophyte metabolite.  Chem Eur J. 2006;  12 4393-4396

Prof. Ren Xiang Tan

Institute of Functional Biomolecules
State Key Laboratory of Pharmaceutical Biotechnology
Nanjing University

Nanjing 210093

People's Republic of China

Phone: + 86 25 83 59 32 01

Fax: + 86 25 83 59 32 01

Email: rxtan@nju.edu.cn

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