Planta Med 2010; 76(16): 1910-1914
DOI: 10.1055/s-0030-1249936
Natural Product Chemistry
Letters
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Chaetoglobosins from the Endophyte Chaetomium globosum

Jie Zhang1 , Hui Ming Ge1 , Rui Hua Jiao1 , Jing Li1 , Hui Peng1 , Yu Rong Wang1 , Jun Hua Wu1 , Yong Chun Song1 , Ren Xiang Tan1
  • 1Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
Further Information

Publication History

received February 4, 2010 revised March 28, 2010

accepted April 16, 2010

Publication Date:
19 May 2010 (online)

Abstract

Two new alkaloids chaetoglobosins V (1) and W (2), together with the six known congeners 38, were isolated through bioassay-guided fractionations from the EtOAc extract of a solid culture of Chaetomium globosum IFB-E041. The structures were elucidated by spectroscopic methods including mainly 1D and 2D NMR techniques. Chaetoglobosin W (2) was unique in its possession of an oxolane ring formed via an oxygen bridge between C-3 and C-6. The isolated fungal metabolites exhibited moderate cytotoxic activities against four human cancer cell lines (KB, K562, MCF-7, and HepG2) with their IC50 values in a range of 18–30 µg/mL.

References

  • 1 Tanenbaum S W. Microbiological, preparative and analytical aspects of cytochalasin production.  Front Biol. 1978;  46 1-14
  • 2 Sekita S, Yoshihira K, Natori S, Kuwano H. Structures of chaetoglobosin A and B, cytotoxic metabolites of Chaetomium globosum.  Tetrahedron Lett. 1973;  23 2109-2112
  • 3 Donoso R, Rivera-Sagred A, Hueso-Rodriguez J, Elson S W. A new chaetoglobosin isolated from a fungus of the genus Discosia.  Nat Prod Lett. 1997;  10 49-54
  • 4 Ichihara A, Katayama K, Teshima H, Oikawa H, Sakamura S. Chateoglobosin O and other phytotoxic metabolites from Cylindrocladium floridanum, a causal fungus of alfalfa black rot disease.  Biosci Biotechnol Biochem. 1996;  60 360-361
  • 5 Andersen B, Semdsgaard J, Frisvad J C. Penicillium expansum: consistent production of patulin, chaetoglobosins, and other secondary metabolites in culture and their natural occurrence in fruit products.  J Agric Food Chem. 2004;  52 2421-2428
  • 6 Wallbrunn C, Luftmann H, Bergander K, Meinhardt F. Phytotoxic chaetoglobosins are produced by the plant pathogen Calonectria morganii (anamorph Cylindrocladium scoparium).  J Gen Appl Microbiol. 2001;  47 33-38
  • 7 Spondlin C, Tamm C. Chaetoglobosin M, a new metabolite of a mutant of Diplodia macrospora, belonging to the family of (1H-indol-3-yl)-substituted 10,11-diethyl-10,11-dinorcytochalasans.  Helv Chim Acta. 1988;  71 1881-1884
  • 8 Burlot L, Cherton J C, Convert O, Correia I, Dennetiere B. New chaetoglobosins from maize infested by Phomopsis leptostromiformis fungi. Production, identification, and semi-synthesis.  Spectroscopy. 2003;  17 725-734
  • 9 Sekita S, Yoshihira K, Natori S, Udagawa S, Sakabe F, Kurata H, Umeda M. Chaetoglobosins, cytotoxic 10-(indol-3-yl)-[13]cytochalasans from Chaetomium spp. I. Production, isolation and some cytological effects of chaetoglobosins A–J.  Chem Pharm Bull. 1982;  30 1609-1617
  • 10 Kang J G, Kim K K, Kang K Y. Antagonism and structural identification of antifungal compound from Chaetomium cochliodes against phytopathogenic fungi.  Agric Chem Biotechnol. 1999;  42 146-150
  • 11 Christian O E, Compton J, Christian K R, Mooberry S L, Valeriote F A, Crews P. Using jasplakinolide to turn on pathways that enable the isolation of new chaetoglobosins from Phomospis asparagi.  J Nat Prod. 2005;  68 1592-1597
  • 12 Qin J C, Zhang Y M, Gao J M, Bai M S, Yang S X, Laatsch H, Zhang A L. Bioactive metabolites produced by Chaetomium globosum, an endophytic fungus isolated from Ginkgo biloba.  Bioorg Med Chem Lett. 2009;  19 1572-1574
  • 13 Ge H M, Yu Z G, Zhang J, Wu J H, Tan R X. Bioactive alkaloids from endophytic Aspergillus fumigatus.  J Nat Prod. 2009;  72 753-755
  • 14 Zhang Y L, Ge H M, Zhao W, Dong H, Xu Q, Li S H, Li J, Zhang J, Song Y C, Tan R X. Unprecedented immunosuppressive polyketides from Daldinia eschscholzii, a mantis-associated fungus.  Angew Chem Int Ed. 2008;  47 5823-5826
  • 15 Jiao R H, Xu S, Liu J Y, Ge H M, Ding H, Xu C, Zhu H L, Tan R X. Chaetominine, a cytotoxic alkaloid produced by endophytic Chaetomium sp. IFB-E015.  Org Lett. 2006;  8 5709-5712
  • 16 Jiao W X, Feng Y J, Blunt J W, Cole A L J, Munro M H G. Chaetoglobosins Q, R, and T, three further new metabolites from Chaetomium globosum.  J Nat Prod. 2004;  67 1722-1725
  • 17 Ding G, Song Y C, Chen J R, Xu C, Ge H M, Wang X T, Tan R X. Chaetoglobosin U, a cytochalasan alkaloid from endophytic Chaetomium globosum IFB-E019.  J Nat Prod. 2006;  69 302-304
  • 18 Sekita S, Yoshihira K, Natori S. Chaetoglobosins, cytotoxic 10-(indol-3-yl)-[13]cytochalasans from Chaetomium spp. IV. Carbon-13 nuclear magnetic resonance spectra and their application to a biosynthetic study.  Chem Pharm Bull. 1983;  31 490-498
  • 19 Sekita S, Yoshihira K, Natori S, Kuwano H. Chaetoglobosins G, and J, cytotoxic indol-3-yl [13]-cytochalasans from Chaetomium globosum.  Tetrahedron Lett. 1977;  32 2771-2774
  • 20 Silverton J V, Akiyama T, Kabuto C. X-Ray analysis of chaetoglobosin A, an indo3-yl-[13] cytochalasan from Chaetomium globosum.  Tetrahedron Lett. 1976;  17 1349-1350
  • 21 Silverton J V, Kabuto C. The structure of Chaetoglobosin A: a novel use of quartet invarians.  Acta Crystallogr B. 1978;  34 588-593
  • 22 Burlot L, Cherton J C, Convert O, Larpent C, Dennetiere B, Dardoize F. Hemisynthesis from chaetoglobosin M. I. Obtention of two new chaetoglobosins by intramolecular Michael reaction under mild basic conditions.  Magn Reson Chem. 1996;  34 538-544
  • 23 Sekita S, Yoshihira K, Natori S. Structures of chaetoglobosins C, D, E, and F, cytotoxic indol-3-yl-[13]cytochalasans from Chaetomium globosum.  Tetrahedron Lett. 1976;  17 1351-1354
  • 24 Oikawa H, Murakami Y, Ichihara A. 20-ketoreductase activity of chaetoglobosin A and prochaetoglobosins in a cell-free system of Chaetomium subaffine and the isolation of new chaetoglobosins.  Biosci Biotechnol Biochem. 1993;  57 628-631
  • 25 Mosman T J. Rapid colorimetric assay for cellular growth and survival: application to proliferation and cytotoxicity assays.  J Immunol Methods. 1983;  65 55-63

Prof. Dr. Ren Xiang Tan

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

22 Hankou Road

Nanjing 210093

People's Republic of China

Phone: + 86 25 83 59 29 45

Fax: + 86 25 83 30 27 28

Email: rxtan@nju.edu.cn

>