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Third Generation Antitumor Platinum(II) Complexes of the [1‐(Fluoro/difluorophenyl)‐2‐phenylethylenediamine]platinum(II) Type
Author(s) -
Gust Ronald,
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.19953280706
Subject(s) - diastereomer , chemistry , platinum , cisplatin , stereochemistry , medicinal chemistry , chemotherapy , biochemistry , catalysis , medicine , surgery
Abstract The diastereomeric 1‐(fluoro/difluorophenyl)‐2‐phenylethylenediamines (4‐fluoro: erythro ‐1/ threo ‐1; 2,4‐difluoro: erythro ‐2/‐ threo ‐2; 2,6‐difluoro: erythro ‐3/ threo ‐3) and the diastereomeric 1‐(4‐fluorophenyl)‐2‐(3‐hydroxyphenyl)ethylenediamines ( erythro ‐4/‐ threo ‐4) were synthesized from appropriately substituted stilbenes by reaction with IN 3 and subsequent LiAlH 4 reduction. Coordination of the 1,2‐diphenylethylenediamines to platinum was carried out by use of K 2 PtI 4 . The water‐soluble aquasulfatoplatinum(II) complexes ( erythro / threo ‐1‐PtSO 4 ‐ erythro / threo ‐4‐PtSO 4 ) were obtained from the diiodoplatinum(II) complexes by reaction with Ag 2 SO 4 . Additionally erythro / threo ‐4‐PtSO 4 and erythro / threo ‐4‐PtSO 4 were transformed into the dichloroplatinum(II) complexes ( erythro / threo ‐1‐PtCl 2 , erythro / threo ‐4‐PtCl 2 ) by treatment with KCl. In contrast to the less effective erythro ‐configurated sulfatoplatinum(II) complexes the threo ‐analogues showed comparable or even superior activities to cisplatin on the human MDA‐MB‐231 breast cancer cell line. On the MXT‐M‐3.2 breast cancer of the mouse only erythro ‐ and threo ‐4‐PtSO 4 caused similar effects like cisplatin. The strong inhibitory effect of the diastereomeric sulfatoplatinum(II) complexes on the P‐388 leukemia of the mouse was equal to that of cisplatin. On the latter tumor threo ‐4‐PtCl 2 was the most active among the less toxic dichloroplatinum(II) derivatives.