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

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 N-2-methyl- and N-1,N-2-dimethyl-l,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 H-1 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 N-2-methylated and N-1,N-2-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. (C) 1997 Elsevier Science S.A.