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Synthesis, Cytotoxicity, and COMPARE Analysis of Ferrocene and [3]Ferrocenophane Tetrasubstituted Olefin Derivatives against Human Cancer Cells
Author(s) -
Görmen Meral,
Pigeon Pascal,
Top Siden,
Hillard Elizabeth A.,
Huché Michel,
Hartinger Christian G.,
de Montigny Frédéric,
Plamont MarieAude,
Vessières Anne,
Jaouen Gérard
Publication year - 2010
Publication title -
chemmedchem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.817
H-Index - 100
eISSN - 1860-7187
pISSN - 1860-7179
DOI - 10.1002/cmdc.201000286
Subject(s) - chemistry , ferrocene , cytotoxicity , prodrug , cisplatin , stereochemistry , olefin fiber , reactivity (psychology) , selectivity , cancer cell lines , combinatorial chemistry , cancer cell , in vitro , cancer , biochemistry , chemotherapy , biology , medicine , alternative medicine , electrode , pathology , electrochemistry , genetics , catalysis
Herein we report the antiproliferative effects of a series of 28 compounds against the MDA‐MB‐231 breast cancer cell line, including the synthesis of seven new [3]ferrocenophanyl and four new ferrocenyl compounds. For each p ‐R‐phenyl substitution pattern investigated, the [3]ferrocenophanyl derivatives were more cytotoxic than the corresponding ferrocenyl derivative, with the highest activity found for compounds with protic substituents. Theoretical calculations of the HOMO–LUMO gap for the molecules in the Fe 3+ oxidation state suggest a higher reactivity for the [3]ferrocenophanyl derivatives. A lead compound from each series, a [3]ferrocenophanyl and a ferrocenyl compound, possessing two phenol groups, were screened against the NCI/DTP 60‐cell‐line panel. The mean activity over all cell lines was better than cisplatin for both compounds, and both compounds showed subpanel selectivity for leukemia, CNS cancer, and renal cancer. Low systemic toxicity and lack of interaction with DNA (when in the reduced form), suggest that the compounds may act as prodrugs.