Third generation antitumor platinum(II) complexes of the [1-(fluoro/difluorophenyl)-2-phenylethylenediamine]platinum(II) type

Article abstract of DOI:10.1002/ardp.19953280706

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 IN₃ and subsequent LiAlH₄ reduction. Coordination of the 1,2-diphenylethylenediamines to platinum was carried out by use of K₂PtI₄. The water-soluble aquasulfatoplatinum(II) complexes (erythro/threo-1-PtSO₄-erythro/threo-4-PtSO₄) were obtained from the diiodoplatinum(II) complexes by reaction with Ag₂SO₄. Additionally erythro/threo-1-PtSO₄ and erythro/threo-4-PtSO₄ were transformed into the dichloroplatinum(II) complexes (erythro/threo-1-PtCl₂, erythro/threo-4-PtCl₂) by treatment with KCl. In contrast to the less effective erythro-configurated sulfatoplatinum(II) complexes the threoanalogues 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-PtSO₄ 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-PtCl₂ was the most active among the less toxic dichloroplatinum(II) derivatives.