Synthesis and Cytotoxicity of Enantiomerically Pure [1,2-Diamino-1-(4-fluorophenyl)-3-methylbutane]platinum(II) Complexes

✍ Scribed by Anja Dullin; Francois Dufrasne; Michael Gelbcke; Ronald Gust

• Book ID: 102806391
• Publisher: John Wiley and Sons
• Year: 2006
• Tongue: English
• Weight: 606 KB
• Volume: 1
• Category: Article
• ISSN: 1860-7179
• DOI: 10.1002/cmdc.200600032

✦ Synopsis

Abstract

A series of leaving group derivatives of enantiomerically pure [1,2‐diamino‐1‐(4‐fluorophenyl)‐3‐methylbutane]platinum(II) complexes were synthesized and tested for cytotoxicity. The enantiomeric purity was determined by ^1^H NMR spectroscopy on the final diamines after derivation with (1__R__)‐myrtenal. For coordination to platinum, the diamines were reacted with K~2~PtI~4~. The treatment of diiodoplatinum(II) complexes (4F‐Ph/__i__Prop‐PtI~2~) with Ag~2~SO~4~ resulted in the sulfatoplatinum(II) complexes (4F‐Ph/__i__Prop‐PtSO~4~), which can be easily transformed to dichloroplatinum(II) complexes (4F‐Ph/__i__Prop‐PtCl~2~) with 2 n HCl. The importance of the leaving groups and the configuration at the diamine ligand on the antiproliferative effects was evaluated on the hormone‐dependent MCF‐7 and the hormone‐independent MDA‐MB 231 breast cancer cell lines as well as the LNCaP/FGC prostate cancer cell line. (R,R)‐4F‐Ph/__i__Prop‐PtCl~2~ was identified as the most active platinum(II) complex. The 3‐methyl group increased antiproliferative effects relative to the [1,2‐diamino‐1‐(4‐fluorophenyl)butane]platinum(II) complexes described in an earlier study.