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.