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.
Enantiomerically pure 1, 2-diamino-1-(4-fluorophenyl)butanes were synthesized by stereoselective procedures. The enantiomeric purity was determined by (1)H NMR spectroscopy after derivatization with (1R)-myrtenal. For the coordination to platinum, the diamines were reacted with K(2)PtI(4). Reaction with Ag(2)SO(4) yielded the respective sulfatoplatinum(II) complexes, which were converted into the dichloroplatinum(II) complexes by treatment with 2 N HCl. The influence of the configuration and the kind of leaving group on the antitumor activity was studied on the MCF-7 and MDA-MB 231 breast cancer cell lines, as well as on the LnCaP/FGC prostate cancer cell line. It was demonstrated that the dichloroplatinum(II) complexes were more active than the respective diiodoplatinum(II) derivatives. Conversion into the sulfatoplatinum(II) complexes further enhanced the antiproliferative effects. The configuration determined the antitumor effects, dependent on the cell line used: MCF-7: (R, R) > (S, S) > (R, S) > (S, R); MDA-MB 231: (S, S) > (R, R) > (R, S) = (S, R); LnCaP/FGC: (S, S) > (R, R) > (R, S) > (S, R).
Dullin
Anja
A
Institute of Pharmacy, Free University of Berlin, Berlin, Germany.
Dufrasne
Francois
F
Gelbcke
Michael
M
Gust
Ronald
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D001943:Breast Neoplasms / Q000473:pathology; D002073:Butanes / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects*; D004354:Drug Screening Assays, Antitumor; D005260:Female; D006801:Humans; D008297:Male; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D011471:Prostatic Neoplasms / Q000473:pathology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship
D000970:Antineoplastic Agents; D002073:Butanes; D009944:Organoplatinum Compounds