Cytotoxicities of three rebeccamycin derivatives in the National Cancer Institute screening of 60 human tumor cell lines.
Among the biologically active indolocarbazoles, rebeccamycin, a microbial metabolite produced by Saccharothrix aerocolonigenes, is a well-known topoisomerase (Topo) I poison. In the course of structure-activity relationship studies on rebeccamycin analogs, we have prepared a large number of indolocarbazole derivatives and have shown that, depending on the structural modifications, the cytotoxic effects may be, or not, directly correlated to DNA binding and Topo I inhibition. This suggests that if DNA binding and Topo I play a part in the biological activity of these compounds, other cellular targets might be involved. This paper reports the results of the antiproliferative activities (evaluated in the National Cancer Institute's in vitro panel of 60 tumor cell lines) and the results of a COMPARE analysis run with rebeccamycin derivatives to identify other potential biological targets for these compounds.
Moreau
Pascale
P
Laboratoire SEESIB, Université Blaise Pascal, UMR 6504 du CNRS, Aubière, France.
Holbeck
Susan
S
Prudhomme
Michelle
M
Sausville
Edward A
EA
D000970:Antineoplastic Agents / Q000494:pharmacology*; D002227:Carbazoles / Q000494:pharmacology*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D007211:Indoles / Q000494:pharmacology*; D021281:Quantitative Structure-Activity Relationship; D059004:Topoisomerase I Inhibitors
D000970:Antineoplastic Agents; D002227:Carbazoles; D007211:Indoles; D059004:Topoisomerase I Inhibitors; C053339:rebeccamycin