Gold-Containing Indoles as Anticancer Agents That Potentiate The Cytotoxic Effects of Ionizing Radiation
Document Type
Article
Publication Date
1-30-2012
Publication Title
Journal of Medicinal Chemistry
Abstract
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.
Recommended Citation
Craig, Sandra; Gao, Lei; Lee, Irene; Gray, Thomas; and Berdis, Anthony J., "Gold-Containing Indoles as Anticancer Agents That Potentiate The Cytotoxic Effects of Ionizing Radiation" (2012). Chemistry Faculty Publications. 252.
https://engagedscholarship.csuohio.edu/scichem_facpub/252
DOI
10.1021/jm2005942
Volume
55
Issue
5
Comments
T.G.G. thanks the National Science Foundation (grant CHE-1057659) and the Alfred P. Sloan Foundation for support.A.J.B. is supported by funding from the National Institutes of Health (CA118408) and the Department of Defense, US Army Medical Research (CA091380).