Water-soluble camptothecin derivatives that are intrinsic topoisomerase I poisons.
[structure: see text] In an effort to improve the water solubility of camptothecin, four 20-O-phosphate and phosphonate analogues have been prepared. These analogues are freely water soluble, stable at physiological pH, and stabilize the human topoisomerase I-DNA covalent binary complex with the same sequence selectivity as camptothecin itself. All four compounds inhibited the growth of yeast expressing human topoisomerase I in an enzyme-dependent fashion.
Rahier
Nicolas J
NJ
Department of Chemistry, University of Virginia, Charlottesville, Virginia 22901, USA.
Eisenhauer
Brian M
BM
Gao
Rong
R
Jones
Shannon H
SH
Hecht
Sidney M
SM
D002166:Camptothecin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry / Q000378:metabolism; D004264:DNA Topoisomerases, Type I / Q000378:metabolism; D006801:Humans; D006863:Hydrogen-Ion Concentration; D015394:Molecular Structure; D012441:Saccharomyces cerevisiae; D012995:Solubility; D059004:Topoisomerase I Inhibitors
D059004:Topoisomerase I Inhibitors; D004247:DNA; D004264:DNA Topoisomerases, Type I; D002166:Camptothecin