A one-pot synthesis and biological activity of ageladine A and analogues

Sudhir R. Shengule, Wendy L. Loa-Kum-Cheung, Christopher R. Parish, Mélina Blairvacq, Laurent Meijer, Youichi Nakao, Peter Karuso

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    Abstract

    A one-pot synthesis of ageladine A and analogues is reported. The key Pictet-Spengler reaction between 2-aminohistamine and aryl aldehydes has been successfully utilized for the synthesis of the natural product and 14 analogues. These compounds were screened for their matrix metalloprotease (MMP) and kinase inhibition to develop the first structure-activity relationship of ageladine A analogues. One compound, which showed significant kinase activity but little MMP inhibitory activity, was found to be highly active in an antiangiogenic screen, suggesting that the angiogenic activity of ageladine A is not associated with MMP inhibition but rather kinase inhibitory activity. Cytotoxicity was excluded as a mode of action by the assay of ageladine A and an analogue against 60 human cell lines.

    Original languageEnglish
    Pages (from-to)2492-2503
    Number of pages12
    JournalJournal of Medicinal Chemistry
    Volume54
    Issue number7
    DOIs
    Publication statusPublished - 2011 Apr 14

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    ASJC Scopus subject areas

    • Molecular Medicine
    • Drug Discovery

    Cite this

    Shengule, S. R., Loa-Kum-Cheung, W. L., Parish, C. R., Blairvacq, M., Meijer, L., Nakao, Y., & Karuso, P. (2011). A one-pot synthesis and biological activity of ageladine A and analogues. Journal of Medicinal Chemistry, 54(7), 2492-2503. https://doi.org/10.1021/jm200039m