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

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.