title: Synthesis and pharmacological evaluation of 1H-imidazoles as ligands for the estrogen receptor and cytotoxic inhibitors of the cyclooxygenase.
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.
authors.affiliation: Institute of Pharmacy, Free University of Berlin, Königin-Luise Strasse 2+4, D-14195 Berlin, Germany.
authors.forename: Thomas
authors.initials: T
authors.lastname: Wiglenda
authors.forename: Ingo
authors.initials: I
authors.lastname: Ott
authors.forename: Brigitte
authors.initials: B
authors.lastname: Kircher
authors.forename: Petra
authors.initials: P
authors.lastname: Schumacher
authors.forename: Daniela
authors.initials: D
authors.lastname: Schuster
authors.forename: Thierry
authors.initials: T
authors.lastname: Langer
authors.forename: Ronald
authors.initials: R
authors.lastname: Gust
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D016861:Cyclooxygenase Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006801:Humans; D007093:Imidazoles / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D008958:Models, Molecular; D009376:Neoplasms, Hormone-Dependent; D011960:Receptors, Estrogen / Q000187:drug effects / Q000235:genetics; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D016861:Cyclooxygenase Inhibitors; D007093:Imidazoles; D011960:Receptors, Estrogen