Synthesis and cytotoxicity of enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)-3-methylbutane]platinum(II) complexes.
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 1H NMR spectroscopy on the final diamines after derivation with (1R)-myrtenal. For coordination to platinum, the diamines were reacted with K2PtI4. The treatment of diiodoplatinum(II) complexes (4F-Ph/iProp-PtI2) 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-methyl group increased antiproliferative effects relative to the [1,2-diamino-1-(4-fluorophenyl)butane]platinum(II) complexes described in an earlier study.
Dullin
Anja
A
Institute of Pharmacy, Free University of Berlin, Königin-Luise-Str. 2+4, 14195 Berlin, Germany.
Dufrasne
Francois
F
Gelbcke
Michael
M
Gust
Ronald
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D045744:Cell Line, Tumor; D002470:Cell Survival / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D013055:Spectrophotometry, Infrared; D013237:Stereoisomerism
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds