Rare Streptomyces sp. polyketides as modulators of K-Ras localisation

Salim, Angela A., Xiao, Xue, Cho, Kwang-Jin, Piggott, Andrew M., Lacey, Ernest, Hancock, John F. and Capon, Robert J. (2014) Rare Streptomyces sp. polyketides as modulators of K-Ras localisation. Organic and Biomolecular Chemistry, 12 27: 4872-4878. doi:10.1039/c4ob00745j

Author Salim, Angela A.
Xiao, Xue
Cho, Kwang-Jin
Piggott, Andrew M.
Lacey, Ernest
Hancock, John F.
Capon, Robert J.
Title Rare Streptomyces sp. polyketides as modulators of K-Ras localisation
Formatted title
Rare Streptomyces sp. polyketides as modulators of K-Ras localisation
Journal name Organic and Biomolecular Chemistry   Check publisher's open access policy
ISSN 1477-0520
Publication date 2014-07-21
Year available 2014
Sub-type Article (original research)
DOI 10.1039/c4ob00745j
Open Access Status Not Open Access
Volume 12
Issue 27
Start page 4872
End page 4878
Total pages 7
Place of publication Cambridge, United Kingdom
Publisher Royal Society of Chemistry
Language eng
Formatted abstract
Chemical investigations of a soil-derived Streptomyces sp. led to the isolation of five new polyketides, (+)-oxanthromicin, (±)-hemi- oxanthromicins A/B, (±)-spiro-oxanthromicin A and oxanthroquinone, and the known alkaloid staurosporine, and the detection of four new metastable analogues, (±)-spiro-oxanthromicins B1/B2/C1/C2. Among the compounds tested, SAR investigations established that the synthetic oxanthroquinone ethyl ester and 3-O-methyl-oxanthroquinone ethyl ester were optimal at mislocalising oncogenic mutant K-Ras from the plasma membrane of intact Madin-Darby canine kidney (MDCK) cells (IC50 4.6 and 1.2 μM), while a sub-EC 50 dose of (±)-spiro-oxanthromicin A was optimal at potentiating (750%) the K-Ras inhibitory activity of staurosporine (IC 50 60 pM). These studies demonstrate that a rare class of Streptomyces polyketide modulates K-Ras plasma membrane localisation, with implications for the future treatment of K-Ras dependent cancers.
Keyword Chemistry, Organic
Q-Index Code C1
Q-Index Status Confirmed Code
Grant ID ARC DP120100183
Institutional Status UQ

Document type: Journal Article
Sub-type: Article (original research)
Collections: Official 2015 Collection
Institute for Molecular Bioscience - Publications
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