Enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)butane]platinum(II) complexes: Synthesis and antitumor activity against MCF-7 and MDA-MB 231 breast cancer and LnCaP/FGC prostate cancer cell lines

摘要

A series of leaving group derivs. of enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)-3-methylbutane]platinum(II) complexes were synthesized and tested for cytotoxicity. The enantiomeric purity was detd. by 1H NMR spectroscopy on the final diamines after derivation with (1R)-myrtenal. For coordination to platinum, the diamines were reacted with K2Ptl4. The treatment of diiodoplatinum(II) complexes (4F-Ph/iProp-Ptl2) with Ag2SO4 resulted in the sulfatoplatinum(II) complexes (4F-Ph/iProp-PtSO4), which can be easily transformed to dichloroplatinum(II) complexes (4F-Ph/iProp-PtCl2) 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/iProp-PtCl2 was identified as the most active platinum(II) complex. The 3-Me group increased antiproliferative effects relative to the [1,2-diamino-1-(4-fluorophenyl)butane]platinum(II) complexes described in an earlier study.