Synthesis, cytotoxicity, and COMPARE analysis of ferrocene and [3]ferrocenophane tetrasubstituted olefin derivatives against human cancer cells.
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 Fe³(+) 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.
Görmen
Meral
M
Chimie ParisTech, Ecole Nationale Supérieure de Chimie de Paris, UMR CNRS, France.
Pigeon
Pascal
P
Top
Siden
S
Hillard
Elizabeth A
EA
Huché
Michel
M
Hartinger
Christian G
CG
de Montigny
Frédéric
F
Plamont
Marie-Aude
MA
Vessières
Anne
A
Jaouen
Gérard
G
D000475:Alkenes / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use / Q000633:toxicity; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D004354:Drug Screening Assays, Antitumor; D005296:Ferrous Compounds / Q000737:chemistry* / Q000627:therapeutic use / Q000633:toxicity; D006801:Humans; D007700:Kinetics; D000075163:Metallocenes; D008968:Molecular Conformation; D009369:Neoplasms / Q000188:drug therapy
D000475:Alkenes; D000970:Antineoplastic Agents; D005296:Ferrous Compounds; D000075163:Metallocenes; C004998:ferrocene