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Luotonin A. A Naturally Occurring Human DNA Topoisomerase I Poison

Luotonin A. A Naturally Occurring Human DNA Topoisomerase I Poison

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

J Am Chem Soc. 2003 Nov 12;125(45):13628-9.

PMID: 14599178

Abstract:

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.

Chemicals Related in the Paper:

Catalog Number	Product Name	Structure	CAS Number	Price
IAR42415766	Luotonin A			Price

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