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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
Author(s) -
Gust Ronald,
Karl Johann,
Faderl Michael,
Schönenberger Helmut
Publication year - 1995
Publication title -
archiv der pharmazie
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.468
H-Index - 61
eISSN - 1521-4184
pISSN - 0365-6233
DOI - 10.1002/ardp.19953280511
Subject(s) - chemistry , stereochemistry , estrogen receptor , estrogen , ethylenediamine , cancer research , medicine , cancer , breast cancer , inorganic chemistry
[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.