Structure activity relationship studies on C2 side chain substituted 1,1-bis(4-methoxyphenyl)-2-phenylalkenes and 1,1,2-tris(4-methoxyphenyl)alkenes.
1,1-bis(4-Methoxyphenyl)-2-phenylalkenes (1a-9a) and 1,1,2-tris(4-methoxyphenyl)alkenes (1b-9b) with various C2-substituents (H (1a, 1b), methyl (2a, 2b), ethyl (3a, 3b), propyl (4a, 4b), butyl (5a, 5b), 2-cyanoethyl (6a, 6b), 3-cyanopropyl (7a, 7b), 3-aminopropyl (8a, 8b), 3-carboxypropyl (9a, 9b)) were tested for cytotoxic effects on hormone dependent MCF-7 cells. The effects were correlated with agonistic and antagonist properties determined on the MCF-7-2a cell line stably transfected with the plasmid ERE(wtc)luc. We demonstrated that the antiproliferative effects did not result from an interaction with the estrogen receptor (ER). The most cytotoxic compounds 5,5-bis(4-methoxyphenyl)-4-phenylpent-4-enylamine (8a) and 4,5,5-tris(4-methoxyphenyl)pent-4-enyl (8b) showed cytocidal effects without having significant agonistic and antagonistic properties.
Gust
Ronald
R
Institut für Pharmazie der FU Berlin, Königin Luise Strasse 2+4, D-14195 Berlin, Germany. rgust@zedat.fu-berlin.de
Lubczyk
Veronika
V
D000475:Alkenes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D001943:Breast Neoplasms / Q000378:metabolism; D002417:Cattle; D002455:Cell Division / Q000187:drug effects; D045744:Cell Line, Tumor; D003600:Cytosol / Q000378:metabolism; D004958:Estradiol / Q000031:analogs & derivatives / Q000378:metabolism; D005260:Female; D006801:Humans; D006900:Hydroxylation; D008156:Luciferases / Q000378:metabolism; D011960:Receptors, Estrogen / Q000819:agonists / Q000037:antagonists & inhibitors / Q000378:metabolism; D013329:Structure-Activity Relationship; D013629:Tamoxifen / Q000031:analogs & derivatives* / Q000494:pharmacology; D014158:Transcription, Genetic; D014162:Transfection; D014599:Uterus / Q000378:metabolism
D000475:Alkenes; D000970:Antineoplastic Agents; D011960:Receptors, Estrogen; D013629:Tamoxifen; C016601:afimoxifene; D004958:Estradiol; D008156:Luciferases