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Use of COMPARE analysis to discover new natural product drugs: Isolation of camptothecin and 9-methoxycamptothecin from a new source

  1. Author:
    Zhou, B. N.
    Hoch, J. M.
    Johnson, R. K.
    Mattern, M. R.
    Eng, W. K.
    Ma, J.
    Hecht, S. M.
    Newman, D. J.
    Kingston, D. G. I.

  2. Author Address

    Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. Virginia Polytech Inst & State Univ, Dept Chem, Blacksburg, VA 24061 USA. SmithKline Beecham Pharmaceut, King Of Prussia, PA 19406 USA. Univ Virginia, Dept Chem, Charlottesville, VA 22901 USA. NCI, Frederick Canc Res & Dev Ctr, Nat Prod Branch, Frederick, MD 21701 USA.
    1. Year: 2000
  2. Journal: Journal of Natural Products
    1. 63
    2. 9
    3. Pages: 1273-1276
  4. Type of Article: Article
  1. Abstract:

    Analysis of cytotoxicity data of extracts from the National Cancer Institute's Active Repository by the COMPARE protocol was carried out using camptothecin as a reference point. Extracts identified by this process were further characterized by a selective yeast bioassay for inhibitors of topoisomerase I and by a biochemical assay for compounds that stabilize the topoisomerase I-DNA covalent binary complex. Five of the extracts were positive in the yeast bioassay, and eight extracts showed activity on the assay that monitors stabilization of the topoisomerase I-DNA complex. Four of the latter extracts were inactive in the yeast bioassay, and thus would not, have been identified as hits without the COMPARE preselection process. One of the extracts, from Pyrenacantha klaineana, was selected for detailed investigation, and fractionation of this extract yielded camptothecin and 9- methoxycamptothecin as the bioactive constituents.

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