Maqola

Luotonin A. A Naturally Occurring Human DNA Topoisomerase I Poison

Ali ÇağırDepartments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901Shannon H. JonesDepartments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901Rong GaoDepartments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901Brian M. EisenhauerDepartments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901Sidney M. HechtDepartments of Chemistry and Biology, University of Virginia, Charlottesville, Virginia 22901

2003en

ABI

Annotatsiya

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.

Hali tarjima qilinmagan

Identifikatorlar

DOI: 10.1021/ja0368857

Iqtiboslar va manbalar

2 ta iqtibos0 ta foydalanilgan manba

Koʻrsatkichlar — AkademScholar