Luotonin A. A naturally occurring human DNA topoisomerase I poison.

Luotonin A. A naturally occurring human DNA topoisomerase I poison. Research Abstract Details 

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Luotonin A. A naturally occurring human DNA topoisomerase I poison. Abstract Text:

Ali Cagir,Shannon H Jones,Rong Gao,Brian M Eisenhauer,Sidney M Hecht,

Luotonin A is a pyrroloquinazolinoquinoline alkaloid isolated from the Chinese herbal medicinal plant Peganum nigellastrum. Although previously shown to exhibit cytotoxicity against the murine leukemia P-388 cell line, the mechanism of action of luotonin A is unknown. Presently, we demonstrate that luotonin A stabilizes the human DNA topoisomerase I-DNA covalent binary complex, affording the same pattern of cleavage as the structurally related topoisomerase I inhibitor camptothecin. Luotonin A also mediated topoisomerase I-dependent cytotoxicity toward Saccharyomyces cerevisiae lacking yeast topoisomerase I, but harboring a plasmid having the human topoisomerase I gene under the control of a galactose promoter. This finding identifies a putative biochemical locus for the cytotoxic action of luotonin A and has important implications for the mechanism of action of camptothecin and the design of camptothecin analogues.

Luotonin A. A naturally occurring human DNA topoisomerase I poison. Publishing Authors By Initials

A Cagir,SH Jones,R Gao,BM Eisenhauer,SM Hecht,

For similar organic chemicals: quinones research abstracts see: organic chemicals: quinones research

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MEDLINE DATE:

Luotonin A. A naturally occurring human DNA topoisomerase I poison. Journal Published:

PUBLICATION TYPE: Research Support, U.S. Gov't,

Journal: Journal of the American Chemical Society

VOLUME: 125

Page Numbers: 13628-9

Journal Abbreviation: J. Am. Chem. Soc.

ISSN: 0002-7863

DAY: 12

MONTH: Nov

YEAR: 2003

Luotonin A. A naturally occurring human DNA topoisomerase I poison. Information

Number of References:

LANGUAGE: eng

NlmUniqueID: 7503056

Luotonin A. A naturally occurring human DNA topoisomerase I poison. Keywords Mesh Terms:

KEYWORDS: Quinones

MESH TERMS: pharmacology

Chemical & Substance for Abstract: Luotonin A. A naturally occurring human DNA topoisomerase I poison. Information

Substance Name: DNA Topoisomerases, Type I

Registry Number: EC 5.99.1.2

Grant and Affiliation Information for Luotonin A. A naturally occurring human DNA topoisomerase I poison.

AFFILIATION: Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.

Country: United States

AGENCY: United States NCI

GRANT: CA78415

ACRONYM: CA

MEDLINETA: J Am Chem Soc

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