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    Nat Prod Rep. 2009 May;26(5):585-601. Epub 2009 Mar 11.

    Isolation, biology and chemistry of the disorazoles: new anti-cancer macrodiolides.

    Source

    Department of Chemistry, University of Pittsburgh, Pittsburgh, Pennsylvania 15260, USA.

    Abstract

    Covering: 1994 to 2008. The disorazoles comprise a family of 29 closely related macrocyclic polyketides isolated in 1994 from the fermentation broth of the gliding myxobacterium Sorangium cellulosum. Disorazoles A1, E and C1 have shown exceptional biological activites toward inhibiting the proliferation of human cancer cell lines in picomolar and nanomolar concentrations through the disruption of microtubule polymerization. This review gives a brief introduction describing the biosynthesis and the significance of the disorazoles as a new class of microtubulin disruptors. Another portion of the review focuses on the biology of the disorazoles, specifically disorazole A1 and C1, and their antiproliferative efficacy against animal and human tumor cell lines, as well as the available SAR data. The majority of the discussion addresses synthetic efforts, including partial syntheses of various disorazoles and a summary of the total synthesis of disorazole C1.

    PMID:
    19387496
    [PubMed - indexed for MEDLINE]
    PMCID:
    PMC2711774
    Free PMC Article

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