Effect of N,N'-diethyl-1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamines on the 7,12-dimethylbenz[a]anthracene-induced mammary carcinoma of the rat.
The syntheses and estrogen receptor affinities of meso- and (+/-)-N,N'-dialkyl-1,2-bis(2,6-dichloro-4-hydroxypheny)ethylenediamines (2) are described. They show high binding affinities in both diastereomeric forms but with a preference for the meso isomer, reaching a RBA value of 8.6 (meso-2b; 17 beta-estradiol = 100). Both stereoisomers of 2b exhibit a strong inhibitory effect on the 7,12-dimethylbenz[alpha]anthracene (DMBA) induced hormone-dependent mammary carcinoma of the Sprague-Dawley rat, reducing the tumor area by 74 (meso-2b) and 24% [(+/-)-2b], respectively, after 4 weeks administration of 6 x 6 (mg/kg)/week. The high uterotrophic potency makes a mode of action likely which corresponds to the effect of high doses of estrogens.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis*; D002733:Chlorophenols / Q000138:chemical synthesis* / Q000494:pharmacology; D003600:Cytosol / Q000378:metabolism; D005029:Ethylenediamines / Q000138:chemical synthesis* / Q000494:pharmacology; D005260:Female; D066298:In Vitro Techniques; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy*; D051379:Mice; D009929:Organ Size / Q000187:drug effects; D051381:Rats; D011919:Rats, Inbred Strains; D011960:Receptors, Estrogen / Q000378:metabolism; D014599:Uterus / Q000187:drug effects
D000970:Antineoplastic Agents; D002733:Chlorophenols; D005029:Ethylenediamines; D011960:Receptors, Estrogen; D015127:9,10-Dimethyl-1,2-benzanthracene