Makaluvamines, marine natural products, are active anti-cancer agents and DNA topo II inhibitors

L. R. Barrows, D. C. Radisky, B. R. Copp, D. S. Swaffar, R. A. Kramer, R. L. Warters, C. M. Ireland

Research output: Contribution to journalArticle

86 Scopus citations

Abstract

The makaluvamines were isolated from a sponge of the genus Zyzzya by following bioactivity against the human colon carcinoma cell line, HCT 116. These compounds have considerable cytotoxic activity. The makaluvamines appear to be acting through inhibition of DNA topoisomerase II. The compounds show enhanced toxicity toward a topoisomerase II-cleavable complex-sensitive cell line, they inhibit topoisomerase II decatenation of kinetoplast DNA in vitro. Makaluvamine C was shown to produce protein-linked DNA double-strand breaks, and makaluvamine A produced DNA double-strand breaks by neutral filter elution in a dose-dependent fashion similar to 4'-(9-acridinylamino)methanesulfon-m-anisidide (m-AMSA). The makaluvamines also increased the life span of nude mice bearing solid tumors of human ovarian cancer cells.

Original languageEnglish (US)
Pages (from-to)333-347
Number of pages15
JournalAnti-Cancer Drug Design
Volume8
Issue number5
StatePublished - Jan 1 1993

Keywords

  • Cytotoxicity
  • Makaluvamines
  • Marine metabolites
  • Pyrroloiminoquinones
  • Topoisomerase II inhibitors

ASJC Scopus subject areas

  • Biochemistry
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Pharmacology
  • Drug Discovery
  • Organic Chemistry

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  • Cite this

    Barrows, L. R., Radisky, D. C., Copp, B. R., Swaffar, D. S., Kramer, R. A., Warters, R. L., & Ireland, C. M. (1993). Makaluvamines, marine natural products, are active anti-cancer agents and DNA topo II inhibitors. Anti-Cancer Drug Design, 8(5), 333-347.