Anticancer metal compounds in NCI's tumor-screening database: putative mode of action

Clustering analysis of tumor cell cytotoxicity profiles for the National Cancer Institute (NCI)'s open compound repository has been used to catalog over 1100 metal or metalloid containing compounds with potential anticancer activity. The molecular features and corresponding reactivity of these...

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Bibliographic Details
Published inBiochemical pharmacology Vol. 69; no. 7; pp. 1009 - 1039
Main Authors Huang, Ruili, Wallqvist, Anders, Covell, David G.
Format Journal Article
LanguageEnglish
Published England Elsevier Inc 01.04.2005
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Summary:Clustering analysis of tumor cell cytotoxicity profiles for the National Cancer Institute (NCI)'s open compound repository has been used to catalog over 1100 metal or metalloid containing compounds with potential anticancer activity. The molecular features and corresponding reactivity of these compounds have been analyzed in terms of properties of their metals, their associated organic components (ligands) and their capacity to inhibit tumor cell growth. Cytotoxic responses are influenced by both the identity of the metal and the properties of its coordination ligand, with clear associations between structural similarities and cytotoxicity. Assignments of mechanisms of action (MOAs) for these compounds could be segregated into four broad response classes according to preference for binding to biological sulfhydryl groups, chelation, generation of reactive oxygen species (ROS), and production of lipophilic ions. Correlations between specific cytotoxic responses and differential gene expression profiles within the NCI's tumor cell panel serve as a validation for candidate biological targets and putative MOA classes. In addition, specific sensitivity toward subsets of metal containing agents has been found for certain tumor cell panels. Taken together, our results expand the knowledge base available for evaluating, designing and developing new metal-based anticancer drugs that may provide the basis for target-specific therapeutics.
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ISSN:0006-2952
1873-2968
DOI:10.1016/j.bcp.2005.01.001