{"refrec":{"BRefID":261947,"RR":"<b>Bonnard, I.; Bontemps, N.; Lahmy, S.; Banaigs, B.; Combaut, G.; Francisco, C.; Colson, P.; Houssier, C.; Waring, M.J.; Bailly, C.</b> (1995). Binding to DNA and cytotoxic evaluation of ascididemin, the major alkaloid from the Mediterranean ascidian <i>Cystodytes dellechiajei</i>. <i>Anti-Cancer Drug Design 10(4)</i>: 333-346","BEntID":253965,"PublicFlag":1,"CheckedFlag":1,"wosflag":null,"vabbflag":null,"RefStringPartII":". <i>Anti-Cancer Drug Design 10(4)</i>: 333-346","DocTypID":16,"DocType":"Journal","MarineFlag":1,"FreshFlag":0,"BrackishFlag":0,"TerrestrialFlag":0,"Authorstring":"Bonnard, I.; Bontemps, N.; Lahmy, S.; Banaigs, B.; Combaut, G.; Francisco, C.; Colson, P.; Houssier, C.; Waring, M.J.; Bailly, C.","OrigTitleTranslFlag":0,"Authorstringtrunc":"Bonnard, I. <i>et al.</i>","Englishabstract":"The isolation of ascididemin from the Mediterranean ascidian Cystodytes dellechiajei is described. This alkaloid consists of a planar pentacyclic chromophore which was investigated for its DNA-binding and cytotoxic properties. Spectroscopic measurements provided evidence that the drug intercalates into DNA. DNase I footprinting assays indicated that the binding of ascididemin to CC-rich sequences is favoured over binding to AT-rich and mixed sequences. Chemical probes were used to detect ligand-induced structural changes in DNA. The alkaloid induces a hyperreactivity of the DNA towards potassium permanganate, but not towards diethylpyrocarbonate, just as is the case with ethidium bromide;; it has little effect on the catalytic activities of topoisomerases I and II. Ascididemin exhibits marked cytotoxicity towards human leukaemic cells in vitro and appears to be practically equally toxic for drug-sensitive and multidrug-resistant cell lines. 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