Cytotoxic estrogens: anilin mustard linked 1,1,2-triphenylbut-1-enes with mammary tumor inhibiting activity.
In order to develop cytotoxic estrogens with a specific effect on hormone-dependent mammary tumors, two 1,1,2-triphenylbut-1-enes with a 4-OH group at one C-1-phenyl ring and a chloro-[4] or bromo-[8] anilin mustard moiety at the other C-1-phenyl ring were synthesized. 4 and 8 exerted strong alkylating activity and an irreversible binding to the estrogen receptor. In spite of relatively low receptor affinities, both anilin mustards exhibited a better effect on a receptor-positive breast cancer cell line as well as on a hormone-dependent mammary carcinoma of the mouse than on a receptor-negative cell line and a hormone-independent mammary carcinoma. Therefore, a selective antitumor activity of 4 and 8 is likely.
Schneider
M R
MR
Schuderer
M L
ML
D000475:Alkenes / Q000138:chemical synthesis* / Q000494:pharmacology; D000814:Aniline Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D055598:Chemical Phenomena; D002621:Chemistry; D045166:Estradiol Congeners / Q000138:chemical synthesis* / Q000494:pharmacology; D006801:Humans; D008325:Mammary Neoplasms, Experimental / Q000473:pathology*; D051379:Mice; D009150:Mustard Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D011960:Receptors, Estrogen / Q000187:drug effects / Q000378:metabolism; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000473:pathology
D000475:Alkenes; D000814:Aniline Compounds; D000970:Antineoplastic Agents; D045166:Estradiol Congeners; D009150:Mustard Compounds; D011960:Receptors, Estrogen