Synthesis and in vitro antitumor activity of platinum acetonimine complexes

The cis- and trans-dichloro- and diiodo-platinum(II) complexes containing two acetonimines (cis- and trans[PtX2{HN=QCH(3))(2)}(2)b 1 and 2 for X = Cl and 1' and 2' for X = 1, respectively) or one acetonimine and one ammine (cis- and trans- [PtX2(NH3) {HN=C(CH3)(2)}], 3 and 4 for X = Cl and 3' and 4' for X = 1, respectively) have been prepared from platinum-ammine precursors by condensation with acetone. Except for the cis-diiodo species, in all other cases the presence of a base was required. A crucial role of the ligand trans to the ammine undergoing condensation with acetone has been disclosed: the greater the trans effect the greater the reactivity. In a panel of human tumor cell lines representative of ovarian, colon, lung, and breast cancers, cis complexes 1 and 3 are less active than cis-DDP (mean IC50 = 20, 12.5, and 2.8 mu M, respectively), whereas trans complexes 2 and 4 are more active than trans-DDP (mean IC50 = 10.6, 26, and 164 mu M, respectively), thus indicating that substitution of acetonimine for one or two ammine ligands determines strikingly different effects depending upon the complex geometry.