title: Synthesis and biological activity of thiazolylindolequinones, analogues of the natural product BE 10988.
abstract: A number of analogues of the naturally occurring thiazolylindolequinone BE 10988, a reported potent inhibitor of topoisomerase II, have been prepared and evaluated. The compounds were synthesized from 4-(benzyloxy)-5-methoxy-1-methylindole by appropriate substitution at the indole 3-position followed by standard thiazole ring-forming reactions. The toxicity of these potentially bioreductively activated indolequinones was measured in Chinese hamster V79 cells under aerobic and hypoxic conditions. In addition, toxicity was measured in a human breast cancer cell line that shows amplification of the topo II alpha gene and hypersensitivity to known topo II inhibitors such as mAMSA and mitoxantrone. Using a DNA decatenation assay, a comparison was also made of the inhibitory effects of BE 10988 and mitoxantrone on topo II activity.
authors.affiliation: Department of Chemistry, Loughborough University of Technology, Leicestershire, U.K.
authors.forename: C J
authors.initials: CJ
authors.lastname: Moody
authors.forename: E
authors.initials: E
authors.lastname: Swann
authors.forename: S
authors.initials: S
authors.lastname: Houlbrook
authors.forename: M A
authors.initials: MA
authors.lastname: Stephens
authors.forename: I J
authors.initials: IJ
authors.lastname: Stratford
mesh_terms: D000332:Aerobiosis; D000818:Animals; D001943:Breast Neoplasms / Q000188:drug therapy; D016466:CHO Cells; D015687:Cell Hypoxia; D006224:Cricetinae; D003412:Cricetulus; D004353:Drug Evaluation, Preclinical; D006367:HeLa Cells; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D011809:Quinones / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship; D013844:Thiazoles / Q000138:chemical synthesis* / Q000494:pharmacology*; D059005:Topoisomerase II Inhibitors; D014407:Tumor Cells, Cultured
chemical_list: D007211:Indoles; D011809:Quinones; D013844:Thiazoles; D059005:Topoisomerase II Inhibitors; C069638:BE 10988