Lei Gao - Gold-Containing Indoles as Anticancer Agents That Potentiate the Cytotoxic Effects of Ionizing Radiation

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  Publication Details (including relevant citation   information):

  Journal of Medicinal Chemistry, 2012,   55, 2437-2451

DOI: 10.1021/jm2005942


    This report describes the design and application of several   distinct gold-containing indoles as anticancer agents. When used   individually, all gold-bearing compounds display cytostatic   effects against leukemia and adherent cancer cell lines. However,   two gold-bearing indoles show unique behavior by increasing the   cytotoxic effects of clinically relevant levels of ionizing   radiation. Quantifying the amount of DNA damage demonstrates that   each gold–indole enhances apoptosis by inhibiting DNA repair.   Both Au(I)–indoles were tested for inhibitory effects against   various cellular targets including thioredoxin reductase, a known   target of several gold compounds, and various ATP-dependent   kinases. While neither compound significantly inhibits the   activity of thioreoxin reductase, both showed inhibitory effects   against several kinases associated with cancer initiation and   progression. The inhibition of these kinases provides a possible   mechanism for the ability of these Au(I)–indoles to potentiate   the cytotoxic effects of ionizing radiation. Clinical   applications of combining Au(I)–indoles with ionizing radiation   are discussed as a new strategy to achieve chemosensitization of   cancer cells.

  Address (URL): http://pubs.acs.org/doi/abs/10.1021/jm2005942?prevSearch=%255BContrib%253A%2BLei %2BGao%255D&searchHistoryKey=