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

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

Cancer Biology

Research output: Contribution to journal › Article › peer-review

87 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 language	English (US)
Pages (from-to)	333-347
Number of pages	15
Journal	Anti-Cancer Drug Design
Volume	8
Issue number	5
State	Published - 1993

Keywords

Cytotoxicity
Makaluvamines
Marine metabolites
Pyrroloiminoquinones
Topoisomerase II inhibitors

ASJC Scopus subject areas

Biochemistry
Oncology
General Biochemistry, Genetics and Molecular Biology
Pharmacology
Drug Discovery
Organic Chemistry

Cite this

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

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.",

keywords = "Cytotoxicity, Makaluvamines, Marine metabolites, Pyrroloiminoquinones, Topoisomerase II inhibitors",

author = "Barrows, {L. R.} and Radisky, {D. C.} and Copp, {B. R.} and Swaffar, {D. S.} and Kramer, {R. A.} and Warters, {R. L.} and Ireland, {C. M.}",

year = "1993",

language = "English (US)",

volume = "8",

pages = "333--347",

journal = "Anti-Cancer Drug Design",

issn = "0266-9536",

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T1 - Makaluvamines, marine natural products, are active anti-cancer agents and DNA topo II inhibitors

AU - Barrows, L. R.

AU - Radisky, D. C.

AU - Copp, B. R.

AU - Swaffar, D. S.

AU - Kramer, R. A.

AU - Warters, R. L.

AU - Ireland, C. M.

PY - 1993

Y1 - 1993

N2 - 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.

AB - 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.

KW - Cytotoxicity

KW - Makaluvamines

KW - Marine metabolites

KW - Pyrroloiminoquinones

KW - Topoisomerase II inhibitors

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AN - SCOPUS:0027366526

SN - 0266-9536

VL - 8

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EP - 347

JO - Anti-Cancer Drug Design

JF - Anti-Cancer Drug Design

IS - 5

ER -

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

Abstract

Keywords

ASJC Scopus subject areas

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