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

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

Research output: Contribution to journalArticle

48 Scopus citations

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.

Original languageEnglish (US)
Pages (from-to)1273-1276
Number of pages4
JournalJournal of Natural Products
Volume63
Issue number9
DOIs
Publication statusPublished - 2000
Externally publishedYes

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ASJC Scopus subject areas

  • Plant Science
  • Chemistry (miscellaneous)
  • Drug Discovery
  • Organic Chemistry
  • Pharmacology

Cite this

Zhou, B. N., Hoch, J. M., Johnson, R. K., Mattern, M. R., Eng, W. K., Ma, J., ... Kingston, D. G. I. (2000). Use of COMPARE analysis to discover new natural product drugs: Isolation of camptothecin and 9-methoxycamptothecin from a new source. Journal of Natural Products, 63(9), 1273-1276. https://doi.org/10.1021/np000058r