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.
Synthesis and in vitro antitumor activity of platinum acetonimine complexes
BOCCARELLI, Angelina;INTINI, Francesco Paolo;COLUCCIA, Mauro;NATILE, Giovanni
2006-01-01
Abstract
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.I documenti in IRIS sono protetti da copyright e tutti i diritti sono riservati, salvo diversa indicazione.
