2-(Hydroxyphenyl)indoles: a new class of mammary tumor inhibiting compounds.
1-Alkyl-4-chloro-2-(2,6-dichloro-4-hydroxyphenyl)-6-hydroxyindoles (4, alkyl = CH3, C2H5, C3H7) were synthesized by thermolysis of the corresponding N,N'-dialkyl-1,2-diphenylethylenediamines and subsequent ether cleavage. They showed an affinity for the estrogen receptor (1% of 17 beta-estradiol) and inhibited the growth of the 9,10-dimethyl-1,2-benz[a]anthracene (DMBA) induced mammary carcinoma of the Sprague-Dawley (SD) rat. The best result was obtained by the ethyl compound (4b), which reduced the original tumor area by 50% after 4 weeks administration of 6 X 18 (mg/kg)/week. Since 4a and 4b show uterotrophic activity and cytostatic effects against hormone-independent cells, a dual mode of action has to be considered for the tumor inhibition.
D015127:9,10-Dimethyl-1,2-benzanthracene; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000627:therapeutic use; D002417:Cattle; D002478:Cells, Cultured; D055598:Chemical Phenomena; D002621:Chemistry; D003619:Dansyl Compounds / Q000138:chemical synthesis / Q000494:pharmacology; D045166:Estradiol Congeners / Q000138:chemical synthesis; D004965:Estrogen Antagonists / Q000138:chemical synthesis; D005260:Female; D006801:Humans; D007211:Indoles / Q000138:chemical synthesis* / Q000494:pharmacology; D008325:Mammary Neoplasms, Experimental / Q000139:chemically induced / Q000188:drug therapy; D008727:Methotrexate / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000494:pharmacology; D051379:Mice; D051381:Rats; D011919:Rats, Inbred Strains; D014599:Uterus / Q000187:drug effects
D000970:Antineoplastic Agents; D003619:Dansyl Compounds; D045166:Estradiol Congeners; D004965:Estrogen Antagonists; D007211:Indoles; D015127:9,10-Dimethyl-1,2-benzanthracene; C047531:D 15413; C037360:N(alpha)-(4-amino-4-deoxy-N(10)-methylpteroyl)-N-(epsilon)-(5-(N,N-dimethylamino)-1-naphthalenesulfonyl)lysine; D008727:Methotrexate