Novel Cytotoxic Topoisomerase II Inhibiting Pyrroloiminoquinones from Fijian Sponges of the Genus Zyzzya

Derek C. Radisky, Evette S. Radisky, Brent R. Copp, Chris M. Ireland, Louis R. Barrows, Robert A. Kramer

Research output: Contribution to journalArticle

201 Scopus citations

Abstract

We present the isolation and characterization of seven novel [natural] pyrroloiminoquinones, the makaluvamines A–F (1–6), makaluvone (7), and the known compounds discorhabdin A (8) and damirone B (9) from the Fijian sponge Zyzzya cf. marsailis. The makaluvamines exhibit potent in vitro cytotoxicity toward the human colon tumor cell-line HCT 116, show differential toxicity toward the topoisomerase II sensitive CHO cell-line xrs-6, and inhibit topoisomerase II in vitro. This activity may be mediated by intercalation into DNA and single-stranded breakage. Makaluvamine A and C exhibited in vivo antitumor activity against the human ovarian carcinoma Ovcar3 implanted in athymic mice. The makaluvamines suggest a plausible interrelationship between the batzelline/isobatzelline and discorhabdin/prianosin classes of compounds.

Original languageEnglish (US)
Pages (from-to)1632-1638
Number of pages7
JournalJournal of the American Chemical Society
Volume115
Issue number5
DOIs
StatePublished - Mar 1 1993

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ASJC Scopus subject areas

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

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