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Actinopolysporins A-C and Tubercidin as a Pdcd4 Stabilizer from the Halophilic Actinomycete Actinopolyspora erythraea YIM 90600

  1. Author:
    Zhao, L. X.
    Huang, S. X.
    Tang, S. K.
    Jiang, C. L.
    Duan, Y. W.
    Beutler, J. A.
    Henrich, C. J.
    McMahon, J. B.
    Schmid, T.
    Blees, J. S.
    Colburn, N. H.
    Rajski, S. R.
    Shen, B.

  2. Author Address

    [Zhao, LX; Rajski, SR; Shen, B] Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA. [Zhao, LX; Tang, SK; Jiang, CL] Yunnan Univ, Yunnan Inst Microbiol, Yunnan 650091, Peoples R China. [Huang, SX; Shen, B] Scripps Florida, Dept Chem, Jupiter, FL 33458 USA. [Shen, B] Scripps Florida, Dept Mol Therapeut, Jupiter, FL 33458 USA. [Shen, B] Scripps Florida, Nat Prod Lib Initiat TSRL, Jupiter, FL 33458 USA. [Huang, SX; Duan, YW] Hunan Engn Res Ctr Combinatorial Biosynth & Nat P, Changsha 410329, Hunan, Peoples R China. [Beutler, JA; Henrich, CJ; McMahon, JB] Mol Targets Lab, Frederick, MD 21702 USA. [Henrich, CJ] SAIC Frederick Inc, Frederick, MD 21702 USA. [Colburn, NH] NCI, Lab Canc Prevent, Frederick, MD 21702 USA. [Schmid, T; Blees, JS] Goethe Univ Frankfurt, Inst Biochem I ZAFES, Fac Med, D-60590 Frankfurt, Germany.;Shen, B (reprint author), Univ Wisconsin, Div Pharmaceut Sci, Madison, WI 53705 USA;shenb@scripps.edu
    1. Year: 2011
    2. Date: Sep
  2. Journal: Journal of Natural Products
    1. 74
    2. 9
    3. Pages: 1990-1995
  4. Type of Article: Article
  5. ISSN: 0163-3864
  1. Abstract:

    Our current natural product program utilizes new actinomycetes originating from unexplored and underexplored ecological niches, employing cytotoxicity against a selected panel of cancer cell lines as the preliminary screen to identify hit strains for natural product dereplication, followed by mechanism-based assays of the purified natural products to discover potential anticancer drug leads. Three new linear polyketides, actinopolysporins A (1), B (2), and C (3), along with the known antineoplastic antibiotic tubercidin (4), were isolated from the halophilic actinomycete Actinopolyspora erythraea YIM 90600, and the structures of the new compounds were elucidated on the basis of spectroscopic data interpretation. All four compounds were assayed for their ability to stabilize the tumor suppressor programmed cell death protein 4 (Pdcd4), which is known to antagonize critical events in oncogenic pathways. Only 4 significantly inhibited proteasomal degradation of a model Pdcd4 luciferase fusion protein, with an IC(50) of 0.88 +/- 0.09 mu M, unveiling a novel biological activity for this well-studied natural product.

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External Sources

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  2. DOI: 10.1021/np200603g
  3. View record in Web of Science®
  4. WOS: 000295100400023

Library Notes

  1. Fiscal Year: FY2011-2012
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