Luotonin A. A naturally occurring human DNA topoisomerase I poison
- J Am Chem Soc. 2003 Nov 12;125(45):13628-9. doi: 10.1021/ja0368857.
- 1. Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.
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.
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Cat. No.Product NameDescriptionTargetResearch Area
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Research Areas: Infection