Organometallic cyclic polyphenols derived from 1,2-(alpha-keto tri or tetra methylene) ferrocene show strong antiproliferative activity on hormone-independent breast cancer cells

Dalton Trans. 2010 Aug 28;39(32):7444-50. doi: 10.1039/c0dt00169d. Epub 2010 Jul 8.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / therapeutic use
  • Benzylidene Compounds / chemistry*
  • Breast Neoplasms / drug therapy*
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Estrogen Receptor alpha / metabolism
  • Estrogen Receptor beta / metabolism
  • Estrogens / metabolism*
  • Female
  • Ferrous Compounds / chemistry*
  • Flavonoids / chemical synthesis
  • Flavonoids / chemistry*
  • Flavonoids / therapeutic use
  • Humans
  • Metallocenes
  • Molecular Conformation
  • Phenols / chemical synthesis
  • Phenols / chemistry*
  • Phenols / therapeutic use
  • Polyphenols

Substances

  • 1,2-(1-(1,1-bis(4-hydroxyphenyl)methylidene)tetramethylene)ferrocene
  • 1,2-(1-(1,1-bis(4-hydroxyphenyl)methylidene)trimethylene)ferrocene
  • Antineoplastic Agents
  • Benzylidene Compounds
  • Estrogen Receptor alpha
  • Estrogen Receptor beta
  • Estrogens
  • Ferrous Compounds
  • Flavonoids
  • Metallocenes
  • Phenols
  • Polyphenols