Modification of the estrogenic properties of diphenols by the incorporation of ferrocene. Generation of antiproliferative effects in vitro.
We report here the synthesis and the strong and unexpected antiproliferative effect of the organometallic diphenolic compound 1,1-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene (4) on both hormone-dependent (MCF7) and -independent (MDA-MB231) breast cancer cells (IC(50) = 0.7 and 0.6 microM). Surprisingly, 6 [1,2-bis(4'-hydroxyphenyl)-2-ferrocenyl-but-1-ene], the regioisomer of 4, shows only a modest effect on these cell lines. This pertinent organometallic modification seems to trigger an intracellular oxidation of the structurally favorable compound 4, leading to the generation of a potent cytotoxic compound.
Vessières
Anne
A
Laboratoire de Chimie et Biochimie des Complexes Moléculaires, UMR CNRS 7576, Ecole Nationale Supérieure de Chimie de Paris, France.
Top
Siden
S
Pigeon
Pascal
P
Hillard
Elizabeth
E
Boubeker
Leila
L
Spera
Daniela
D
Jaouen
Gérard
G
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms; D045744:Cell Line, Tumor; D047628:Estrogen Receptor alpha / Q000737:chemistry / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000737:chemistry / Q000378:metabolism; D004967:Estrogens / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D005260:Female; D005296:Ferrous Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D066298:In Vitro Techniques; D000075163:Metallocenes; D009376:Neoplasms, Hormone-Dependent; D009942:Organometallic Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D010636:Phenols / Q000138:chemical synthesis* / Q000737:chemistry* / Q000494:pharmacology; D013329:Structure-Activity Relationship; D014599:Uterus / Q000378:metabolism
C501751:1,1-bis(4'-hydroxyphenyl)-2-ferrocenylbut-1-ene; D000970:Antineoplastic Agents; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D005296:Ferrous Compounds; D000075163:Metallocenes; D009942:Organometallic Compounds; D010636:Phenols; C004998:ferrocene