Copyright © 2014 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim
October 26, 2010
VIP: Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells
Meral Görmen, Pascal Pigeon, Siden Top,* Elizabeth A. Hillard,* Michel Huché, Christian G. Hartinger, Frédéric de Montigny, Marie-Aude Plamont, Anne Vessières, Gérard Jaouen
The development of organometallic compounds as anticancer agents is a quickly growing field in bioinorganic chemistry. A collaborative research effort led by Elizabeth Hillard and Siden Top at the Ecole Nationale Supérieure de Chemie in Paris (France) used a 28-compound library for a structure–activity relationship study. They showed that ferrocenophanes with protic phenyl substituents are more active than those with non-protic substitution, and are also more active than their ferrocene analogues. Their observations are consistent with their proposed mechanism of oxidative activation, which is furthermore supported by HOMO–LUMO energy gap calculations.
Two of these compounds, which were selected for screening against the NCI/DPT 60-human tumor cell line panel, were shown to have a broad spectrum of activity, with full-panel average values lower than that of cisplatin. The team's analysis suggests DNA alkylation or DNA metabolites as possible mechanisms of toxicity, and systemic toxicity studies as well as nucleoside interaction studies suggest that the compounds have prodrug behavior. These molecules exhibit some of the lowest IC50 values ever reported for organometallic compounds against cancer cells.
Received July 13, 2010; published online October 14, 2010, DOI: 10.1002/cmdc.201000286.