Document Report Card

ID: ALA1128261

Journal: J Med Chem

Title: Synthesis and biological activity of thiazolylindolequinones, analogues of the natural product BE 10988.

Authors: Moody CJ, Swann E, Houlbrook S, Stephens MA, Stratford IJ.

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.

CiteXplore: 7699696

DOI: 10.1021/jm00006a024