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Planta Med 2011; 77(18): 2057-2060
DOI: 10.1055/s-0031-1280097
Natural Product Chemistry
Letters
© Georg Thieme Verlag KG Stuttgart · New York

Cytotoxic Angucyclines from Amycolatopsis sp. HCa1, a Rare Actinobacteria Derived from Oxya chinensis

Zhi Kai Guo1 , Ting Wang1 , Ye Guo1 , Yong Chun Song1 , Ren Xiang Tan1 , Hui Ming Ge1 , 2
  • 1Institute of Functional Biomolecules, State Key Laboratory of Pharmaceutical Biotechnology, Nanjing University, Nanjing, China
  • 2State Key Laboratory of Bioreactor Engineering, East China University of Science & Technology, Shanghai, China
Further Information

Publication History

received February 20, 2011 revised June 18, 2011

accepted June 28, 2011

Publication Date:
09 August 2011 (online)

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Abstract

Two new angucyclines, named (2R,3R)-2-hydroxy-8-O-methyltetrangomycin (1) and (2R,3R)-2-hydroxy-5-O-methyltetrangomycin (2), together with eight known compounds (3–10), were isolated from the culture of Amycolatopsis sp. HCa1, a rare actinobacteria isolated from the gut of Oxya chinensis. The new structures were elucidated through extensive spectroscopic data analysis, and their absolute configurations were assigned by application of the modified Mosher's method and CD spectrum comparison. Their in vitro cytotoxic activities against four cell lines including human cervical cancer cell line (HeLa), human gastric adenocarcinoma cell line (SGC-7901), human lung adenocarcinoma cell line (SPC-A-1), and mouse macrophage cell line (RAW264.7) were then investigated. Compounds 3, 4, 9, and 10 showed potent cytotoxic activities towards the HeLa cells with IC50 values of 0.27, 0.11, 0.56, and 0.39 µM, respectively.

Key words

Amycolatopsis - Pseudonocardiaceae - Oxya chinensis - angucycline - cytotoxicity

Supporting Information

References

  • 1 Oh D C, Poulsen M, Currie C R, Clardy J. Dentigerumycin: a bacterial mediator of an ant-fungus symbiosis.  Nat Chem Biol. 2009;  5 391-393
    CrossrefPubMedSearch in Google Scholar
  • 2 Scott J J, Oh D C, Yuceer M C, Klepzig K D, Clardy J, Currie C R. Bacterial protection of beetle-fungus mutualism.  Science. 2008;  322 63
    CrossrefPubMedSearch in Google Scholar
  • 3 Currie C R, Scott J A, Summerbell R C, Malloch D. Fungus-growing ants use antibiotic-producing bacteria to control garden parasites.  Nature. 1999;  398 701-704
    CrossrefPubMedSearch in Google Scholar
  • 4 Iwai K, Iwamoto S, Aisaka K, Suzuki M. Isolation of novel actinomycetes from spider materials.  Actinomycetologica. 2009;  23 8-15
    CrossrefPubMedSearch in Google Scholar
  • 5 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
    CrossrefPubMedSearch in Google Scholar
  • 6 Kunimoto S, Lu J, Esumi H, Yamazaki Y, Kinoshita N, Honma Y, Hamada M, Ohsono M, Ishizuka M, Takeuchi T. Kigamicins, novel antitumor antibiotics. I. Taxonomy, isolation, physico-chemical properties and biological activities.  J Antibiot. 2003;  56 1004-1011
    CrossrefPubMedSearch in Google Scholar
  • 7 Matsumoto N, Tsuchida T, Sawa R, Iinuma H, Nakamura H, Naganawa H, Sawa T, Takeuchi T. Epoxyquinomicins A, B, C and D, new antibiotics from Amycolatopsis. III. Physico-chemical properties and structure determination.  J Antibiot. 1997;  50 912-915
    CrossrefPubMedSearch in Google Scholar
  • 8 Tsuchida T, Sawa R, Takahashi Y, Iinuma H, Sawa T, Naganawa H, Takeuchi T. Azicemicins A and B, new antimicrobial agents produced by Amycolatopsis. II. Structure determination.  J Antibiot. 1995;  48 1148-1152
    CrossrefPubMedSearch in Google Scholar
  • 9 Zhu L L, Ostash B, Rix U, Nur-e-Alam M, Mayers A, Luzhetskyy A, Mendez C, Salas J A, Bechthold A, Fedorenko V, Rohr J. Identification of the function of gene lndM2 encoding a bifunctional oxygenase-reductase involved in the biosynthesis of the antitumor antibiotic landomycin E by Streptomyces globisporus 1912 supports the originally assigned structure for landomycinone.  J Org Chem. 2005;  70 631-638
    CrossrefPubMedSearch in Google Scholar
  • 10 Kuntsmann M P, Mitscher L A. The structural characterization of tetrangomycin and tetrangulol.  J Org Chem. 1966;  31 2920-2925
    CrossrefPubMedSearch in Google Scholar
  • 11 Kern D L, Schaumberg J P, Hokanson G C, French J C. PD 116 779, a new antitumor antibiotic of the benz[α]anthraquinone class.  J Antibiot. 1986;  39 469-470
    CrossrefPubMedSearch in Google Scholar
  • 12 Yamashita N, Harada T, Shin-Ya K, Seto H. 6-Hydroxytetrangulol, a new CPP32 protease inducer produced by Streptomcyces sp.  J Antibiot. 1998;  51 79-81
    CrossrefPubMedSearch in Google Scholar
  • 13 Maehr H, Liu C M, Liu M, Perrotta A, Smallheer J M, Williams T H, Blount J F. Microbial products. VI. Five novel metabolites related to benz[α]anthracene from an unidentified actinomycete designated X-14881.  J Antibiot. 1982;  35 1627-1631
    CrossrefPubMedSearch in Google Scholar
  • 14 Gould S J, Cheng X C. New benz[α]anthraquinone secondary metabolites from Streptomyces phaeochromogenes.  J Org Chem. 1994;  59 400-405
    CrossrefPubMedSearch in Google Scholar
  • 15 Irie H, Mizuno Y, Kouno I, Nagasawa T, Tani Y, Yamada H, Taga T, Osaki K. Structures of new antibiotic substances, Sakyomicin A, B, C and D; X-ray crystal and molecular structure of Sakyomicin A.  J Chem Soc Chem Commun. 1983;  174-175
    PubMedSearch in Google Scholar
  • 16 Li E W, Tian R R, Liu S C, Chen X L, Guo L D, Che Y S. Pestalotheols A–D, bioactive metabolites from the plant endophytic fungus Pestalotiopsis theae.  J Nat Prod. 2008;  71 664-668
    CrossrefPubMedSearch in Google Scholar
  • 17 Rohr J, Thiericke R. Angucycline group antibiotics.  Nat Prod Rep. 1992;  9 103-137
    CrossrefPubMedSearch in Google Scholar
  • 18 Shigihara Y, Koizumi Y, Tamamura T, Homma Y, Isshiki K, Dobashi K, Naganawa H, Takeuchi T. 6-Deoxy-8-O-methylrabelomycin and 8-O-methylrabelomycin from a Streptomyces species.  J Antibiot. 1988;  41 1260-1264
    CrossrefPubMedSearch in Google Scholar
  • 19 Gilpin M L, Balchin J, Box S J, Tyler J W. MM 47755, a new benz[α]anthracene antibiotic from a Streptomycete.  J Antibiot. 1989;  42 627-628
    CrossrefPubMedSearch in Google Scholar
  • 20 Kesenheimer C, Groth U. Total synthesis of (-)-8-O-methyltetrangomycin (MM 47755).  Org Lett. 2006;  8 2507-2510
    CrossrefPubMedSearch in Google Scholar
  • 21 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
    CrossrefPubMedSearch in Google Scholar

Assoc. Prof. Dr. Hui Ming Ge

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

22 Hankou Road

Nanjing 210093

China

Phone: +86 25 83 59 32 01

Fax: +86 25 83 59 32 01

Email: hmge@nju.edu.cn