title: Organometallic cyclic polyphenols derived from 1,2-(alpha-keto tri or tetra methylene) ferrocene show strong antiproliferative activity on hormone-independent breast cancer cells.
abstract: We have previously shown that achiral ferrocenyl diphenol butene derivatives are strong antitumor agents against both hormone-dependent and -independent breast cancer cell lines. We report now examples of a new series of two planar chiral diphenol derivatives, namely 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]trimethylene] ferrocene (4), and 1,2-[1-[1,1-bis(4-hydroxyphenyl)methylidene]tetramethylene]ferrocene (5). They were prepared under racemic form from a McMurry coupling reaction with 30% and 16% yields, respectively. Compound 5 gave crystals suitable for X-ray structural analysis. Compounds 4 and 5 were tested for ERalpha and ERbeta affinity, lipophilicity, and proliferative/antiproliferative effects against the hormone-dependent breast cancer cell line MCF-7, and the hormone-independent breast cancer cell line MDA-MB-231. Both compounds exhibit better affinity for ERbeta (16.4 +/- 0.1, and 7.0 +/- 0.4, respectively) than for ERalpha (6.4 +/- 0.2, and 6.6 +/- 0.2). The test on hormone-independent breast cancer cell line MDA-MB-231 showed that 4 with a 5-membered ring gives an IC50 value of 2.7 microM while with 5 in which the ring has 6 carbons, the value is reduced to IC50 = 1.23 microM.
authors.affiliation: Chimie ParisTech (Ecole Nationale Supérieure de Chimie de Paris), Laboratoire Charles Friedel, UMR CNRS 7223, 11 rue P. et M. Curie, 75231, Paris cedex 05, France.
authors.forename: Damian
authors.initials: D
authors.lastname: Plazuk
authors.forename: Siden
authors.initials: S
authors.lastname: Top
authors.forename: Anne
authors.initials: A
authors.lastname: Vessières
authors.forename: Marie-Aude
authors.initials: MA
authors.lastname: Plamont
authors.forename: Michel
authors.initials: M
authors.lastname: Huché
authors.forename: Janusz
authors.initials: J
authors.lastname: Zakrzewski
authors.forename: Anna
authors.initials: A
authors.lastname: Makal
authors.forename: Krzysztof
authors.initials: K
authors.lastname: Woźniak
authors.forename: Gérard
authors.initials: G
authors.lastname: Jaouen
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D001597:Benzylidene Compounds / Q000737:chemistry*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D018360:Crystallography, X-Ray; D047628:Estrogen Receptor alpha / Q000378:metabolism; D047629:Estrogen Receptor beta / Q000378:metabolism; D004967:Estrogens / Q000378:metabolism*; D005260:Female; D005296:Ferrous Compounds / Q000737:chemistry*; D005419:Flavonoids / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D006801:Humans; D000075163:Metallocenes; D008968:Molecular Conformation; D010636:Phenols / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use; D059808:Polyphenols
chemical_list: C553825:1,2-(1-(1,1-bis(4-hydroxyphenyl)methylidene)tetramethylene)ferrocene; C553824:1,2-(1-(1,1-bis(4-hydroxyphenyl)methylidene)trimethylene)ferrocene; D000970:Antineoplastic Agents; D001597:Benzylidene Compounds; D047628:Estrogen Receptor alpha; D047629:Estrogen Receptor beta; D004967:Estrogens; D005296:Ferrous Compounds; D005419:Flavonoids; D000075163:Metallocenes; D010636:Phenols; D059808:Polyphenols