2-phenyl-1-[4-(2-piperidine-1-yl-ethoxy)benzyl]-1H-benzimidazoles as ligands for the estrogen receptor: synthesis and pharmacological evaluation.
2-phenyl-1H-benzimidazoles 7a-e were synthesized and tested for gene activation on ERalpha-positive MCF-7 breast cancer cells, stably transfected with the reporter plasmid EREwtcluc (MCF-7-2a cells). None of the compounds showed agonistic properties, but they antagonized dependent on hydroxyl groups at the benzimidazole core (5- or 6-OH) and at the aromatic ring in the 2-position (4-OH) in high concentrations the gene activation induced by estradiol (E2, 1 nM). All compounds exhibited significant antiproliferative properties on MCF-7 cells but they were inactive against hormone independent, ER negative MDA-MB-231 cells.
Dettmann
Sandra
S
Institut für Pharmazie, Freie Universität Berlin, Königin-Luise-Str. 2+4, D-14195 Berlin, Germany.
Szymanowitz
Katrin
K
Wellner
Anja
A
Schiedel
Anke
A
Müller
Christa E
CE
Gust
Ronald
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001562:Benzimidazoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000188:drug therapy*; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D047629:Estrogen Receptor beta / Q000235:genetics* / Q000378:metabolism; D005260:Female; D015972:Gene Expression Regulation, Neoplastic / Q000187:drug effects*; D006801:Humans
D000970:Antineoplastic Agents; D001562:Benzimidazoles; D047629:Estrogen Receptor beta