Synthesis and pharmacological evaluation of 1H-imidazoles as ligands for the estrogen receptor and cytotoxic inhibitors of the cyclooxygenase

J Med Chem. 2005 Oct 6;48(20):6516-21. doi: 10.1021/jm050190u.

Abstract

The 1H-imidazoles 7a-e were synthesized and tested for biological activity in vitro. The results pointed to a clear structure-activity relationship. The introduction of an ethyl chain at C5 of the 1,2,4-tris(4-hydroxyphenyl)-1H-imidazole 7a caused hormonal activity in estrogen receptor positive MCF-7-2a cells. An o-chlorine substituent in the phenolic rings at C2 and C4 as realized in 7b and 7c increased the antiproliferative effects against human breast cancer cell lines MCF-7 and MDA-MB 231. Additionally, both compounds showed strong inhibitory effects on cyclooxygenase enzymes. Therefore, a mode of action including the interference in the arachidonic acid cascade might be possible.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cyclooxygenase Inhibitors / chemical synthesis*
  • Cyclooxygenase Inhibitors / chemistry
  • Cyclooxygenase Inhibitors / pharmacology
  • Humans
  • Imidazoles / chemical synthesis*
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Models, Molecular
  • Neoplasms, Hormone-Dependent
  • Receptors, Estrogen / drug effects
  • Receptors, Estrogen / genetics
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Cyclooxygenase Inhibitors
  • Imidazoles
  • Receptors, Estrogen