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

✍ Scribed by Ronald Gust; Johann Karl; Michael Faderl; Helmut Schönenberger

• Publisher: John Wiley and Sons
• Year: 1995
• Tongue: English
• Weight: 642 KB
• Volume: 328
• Category: Article
• ISSN: 0365-6233
• DOI: 10.1002/ardp.19953280511

✦ Synopsis

Abstract

[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.