title: Calothrixins, a new class of human DNA topoisomerase I poisons.
abstract: Calothrixins A (1) and B (2) were converted to their O- and N-methylated derivatives, respectively. All four compounds were found to act as poisons of DNA topoisomerase I and to do so reversibly. Three of the calothrixins (1-3) were tested for their cytotoxicity toward cultured (p53 proficient) CEM leukemia cells and found to exhibit IC(50) values ranging from 0.20 to 5.13 muM. The cell cycle effects of calothrixins 1-3 were also studied. Calothrixin B (2) produced G(1) arrest at 0.1 muM concentration, while higher concentrations of calothrixins 1 and 3 resulted in cell accumulation in both the S and G(2)/M phases of the cell cycle. The cell cycle effects produced by the calothrixins were more readily reversible upon removal of the compounds than those produced by camptothecin.
authors.affiliation: Center for BioEnergetics, Biodesign Institute, Arizona State University, Tempe, Arizona 85287, USA.
authors.forename: Qasim A
authors.initials: QA
authors.lastname: Khan
authors.forename: Jun
authors.initials: J
authors.lastname: Lu
authors.forename: Sidney M
authors.initials: SM
authors.lastname: Hecht
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002453:Cell Cycle / Q000187:drug effects*; D004261:DNA Replication / Q000187:drug effects; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D026121:Indole Alkaloids / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D015394:Molecular Structure; D059004:Topoisomerase I Inhibitors
chemical_list: D000970:Antineoplastic Agents; D026121:Indole Alkaloids; D059004:Topoisomerase I Inhibitors; C418328:calothrixin A; C418327:calothrixin B