Synthesis of A83586C analogs with potent anticancer and beta-catenin/ TCF4/osteopontin inhibitory effects and insights into how A83586C modulates E2Fs and pRb.

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    • Karl J Hale
    • S. Manaviazar
    • L. Lazarides
    • J. George
    • M.A. Walters
    • J. Cai
    • V.M. Delisser
    • G.S. Bhatia
    • S.A. Peak
    • S.M. Dalby
    • A. Lefranc
    • Y.P. Chen
    • A.W. Wood
    • Paul Crowe
    • Pauline Erwin
    • Mohamed El-Tanani

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    The synthesis of three potent new antitumor agents is described: the A83586C-citropeptin hybrid (1), the A83586C-GE3 hybrid (2), and l-Pro-A83586C (3). Significantly, compounds 1 and 2 function as highly potent inhibitors of ß-catenin/TCF4 signaling within cancer cells, while simultaneously downregulating osteopontin (Opn) expression. A83586C antitumor cyclodepsipeptides also inhibit E2F-mediated transcription by downregulating E2F1 expression and inducing dephosphorylation of the oncogenic hyperphosphorylated retinoblastoma protein (pRb).

    DOI

    Original languageEnglish
    Number of pages4
    Pages (from-to)737-740
    JournalOrganic Letters
    Journal publication date05 Feb 2009
    Issue number3
    Volume11
    DOIs
    Publication statusPublished - 05 Feb 2009

    ID: 544986