Synthesis and antitumor activity of enantiomerically pure [1,2-diamino-1-(4-fluorophenyl)propane]dichloroplatinum(II) complexes.
Enantiomerically pure 1, 2-diamino-1-(4-fluorophenyl)propanes were synthesized by stereospecific and stereoselective procedures by use of the (1R, 2S)- and (1S, 2R)-2-amino-1-(4-fluorophenyl)propanols (12a) as intermediates. The enantiomeric purity was determined by (1)H NMR spectroscopy after conversion of the propanolamines and the diamines with (1R)-myrtenal into mono- and diimines. For the coordination to platinum the diamines were reacted with K(2)PtCl(4). The resulting dichloroplatinum(II) complexes 4F-Ph/Me-PtCl(2) were tested for antiproliferative activity on the MCF-7 breast cancer cell line. (SS)- and (RR)-4F-Ph/Me-PtCl(2) produced the strongest inhibitory effect. Both complexes showed cytocidal effects, (SS)-4F-Ph/Me-PtCl(2) even in a concentration of 1 microM. The (1S, 2R)- and (1R, 2S)-configurated complexes were far less active (SS > RR > RS = SR) and comparable in this respect with the standard cisplatin.
Dufrasne
Francois
F
Laboratoire de Chimie Pharmaceutique Organique, Institut de Pharmacie, Université Libre de Bruxelles, Bruxelles, Belgium.
Gelbcke
Michael
M
Schnurr
Beate
B
Gust
Ronald
R
D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000494:pharmacology; D002455:Cell Division / Q000187:drug effects; D015195:Drug Design; D004354:Drug Screening Assays, Antitumor; D006801:Humans; D009944:Organoplatinum Compounds / Q000138:chemical synthesis* / Q000494:pharmacology; D013237:Stereoisomerism; D013329:Structure-Activity Relationship; D014407:Tumor Cells, Cultured / Q000187:drug effects
D000970:Antineoplastic Agents; D009944:Organoplatinum Compounds