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The stereoselectivity of antitumor active [1,2-diamino-1-phenylpropane]dichloroplatinum(II) complexes

par Gust, Ronald;Gelbcke, Michel ;Angermaier, Bernhard;Bachmann, Helmut;Krauser, Rudolf;Schönenberger, Helmut
Référence Inorganica Chimica Acta, 264, 1-2, page (145-160)
Publication Publié, 1997-11

Article révisé par les pairs

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Résumé :

The syntheses of enantiomeric threo-and erythro-1,2-diamino-1-phenylpropanes (Ph/Me) and of the racemic 1,2-diaminophenylethane (Ph/H) are described. These diamines and related N2-methyl-and N1,N2-dimethyl-1,2-diamino-1-phenylpropanes were transformed into dichloroplatinum(II) complexes (Ph/H-PtCl2, Ph/Me-PtCl2, Ph/Me-Me-PtCl2, Ph/Me-Dime-PtCl2). For the 1H NMR spectroscopical determination of their optical purity the diamines (Ph/Me) were converted with (R)-myrtenal into their diimines. In the test on the MCF-7 breast cancer cell line (R,R)-Ph/Me-PtCl2 produced the strongest effect of all new complexes, comparable with that of the standard cisplatin and of other Pt complexes. Its enantiomer (S,S)-Ph/Me-PtCl2 possessed a distinctly weaker inhibitory potency while the erythro-configurated counterparts were even less active [(R,R) > (S,S) > (S,R) = (R,S)]. All N2-methylated and N1,N2-dimethylated complexes (Ph/Me-Me-PtCl2, Ph/Me-Dime-PtCl2) showed comparable activities equaling those of (R,S)-and (S,R)-Ph/Me-PtCl2. The molecular reasons for the differing potencies of the diastereomeric and enantiomeric Ph/Me-PtCl2 complexes are discussed in consideration of the complex conformation. © 1997 Elsevier Science S.A.