Reduction of the estrogenic side effects of the mammary tumor-inhibiting drug [1,2-bis(2,6-dichloro-4-hydroxyphenyl)ethylenediamine]dichloroplatinum(II) by variation of ring substituents

Abstract

[1,2-Bis(4-methoxy/4-hydroxyphenyl)ethylenediamine]dichloroplatinum-(II) complexes were tested on the MDA-MB 231 breast cancer cell line, the lymphocytic leukemia P388, and the estrogen receptor-pos. and -neg. MXT mammary carcinoma of the mouse (MXT,ER(+)-MC, MXT,ER(-)-MC). The comparison of the effects of methoxy-substituted complexes with those of the resp. hydroxy-substituted ones shows that a redn. of estrogenic effects as well as a total loss of the mammary tumor-inhibiting activity takes place on methylation of the 4-OH group. The exchange of the 2,6-standing chlorine atoms by Me groups led to a non-estrogenic compd. which was highly effective against MXT,ER(+)-MC cells and which also proved to be cytotoxic against ER(-)-tumors such as MXT,ER(-)-MC and the P 388 leukemia.