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

[1,2‐Bis(4‐methoxy/4‐hydroxyphenyl)ethylenediamine]dichloroplatinum‐(II) complexes with Cl‐, CH 3 ‐, or OCH 3 ‐substituents in the ortho ‐positions of the aromatic rings ( meso ‐ 1 ‐PtCl 2 , D,L ‐ 1 ‐PtCl 2 , meso ‐ 2 ‐PtCl 2 , D,L ‐ 2 ‐PtCl 2 , meso ‐ 3 ‐PtCl 2 , meso ‐ 4 ‐PtCl 2 , meso ‐ 5 ‐PtCl 2 ) were tested on the MDA‐MB 231 breast cancer cell line, the lymphocytic leukemia P388, and the estrogen receptor‐positive and ‐negative MXT mammary carcinoma of the mouse (MXT,ER(+)‐MC, MXT,ER(−)‐MC). The comparison of the effects of methoxy‐substituted complexes ( meso ‐ 1 ‐PtCl 2 , D,L ‐ 1 ‐PtCl 2 , meso ‐ 3 ‐PtCl 2 ) with those of the respective hydroxy‐substituted ones ( meso ‐ 2 ‐PtCl 2 , D,L ‐ 2 ‐PtCl 2 , meso ‐ 4 ‐PtCl 2 ) shows that a reduction 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 methyl groups in meso ‐ 2 ‐PtCl 2 led to the non‐estrogenic, but on the MXT,ER(+)‐MC highly effective derivative meso ‐ 4 ‐PtCl 2 which proved to be also cytotoxic on ER(−)‐tumors such as MXT,ER(−)‐MC, and the P 388 leukemia.