Makaluvamines, marine natural products, are active anti-cancer agents and DNA topo II inhibitors.
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.
Barrows
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Department of Pharmacology and Toxicology, University of Utah, Salt Lake City 84112.
Radisky
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DC
Copp
B R
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Swaffar
D S
DS
Kramer
R A
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Warters
R L
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Ireland
C M
CM
D000818:Animals; D000970:Antineoplastic Agents / Q000494:pharmacology*; D016466:CHO Cells; D003110:Colonic Neoplasms / Q000188:drug therapy; D006224:Cricetinae; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D007942:Leukemia, Experimental / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D008815:Mice, Inbred Strains; D008819:Mice, Nude; D009368:Neoplasm Transplantation; D010051:Ovarian Neoplasms / Q000188:drug therapy; D011161:Porifera / Q000737:chemistry*; D011758:Pyrroles / Q000302:isolation & purification / Q000494:pharmacology*; D011809:Quinones / Q000302:isolation & purification / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D011758:Pyrroles; D011809:Quinones; D059005:Topoisomerase II Inhibitors