Prev. Article Next Article Table of Contents

Article

Synthesis and in Vitro Antitumor Activity of Platinum Acetonimine Complexes

Supporting Info

Angelina Boccarelli,^† Francesco P. Intini,^‡ Rossella Sasanelli,^† Maria F. Sivo,^‡ Mauro Coluccia,^† and Giovanni Natile*^‡

Dipartimento di Scienze Biomediche ed Oncologia Umana, University of Bari, piazza G. Cesare 11, 70124 Bari, Italy, and Dipartimento Farmaco-Chimico, University of Bari, via E. Orabona 4, 70125 Bari, Italy

J. Med. Chem., 2006, 49 (2), pp 829–837

DOI: 10.1021/jm050986t

Publication Date (Web): January 4, 2006

†

Dipartimento di Scienze Biomediche ed Oncologia Umana.

‡

Dipartimento Farmaco-Chimico.

Corresponding author. Tel: +39-080-5442774. Fax: +39-080-5442230. E-mail: natile@farmchim.uniba.it.

Abstract

The cis- and trans-dichloro- and diiodo-platinum(II) complexes containing two acetonimines (cis- and trans-[PtX₂{HNC(CH₃)₂}₂], 1 and 2 for X = Cl and 1‘ and 2‘ for X = I, respectively) or one acetonimine and one ammine (cis- and trans-[PtX₂(NH₃){HNC(CH₃)₂}], 3 and 4 for X = Cl and 3‘ and 4‘ for X = I, 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 μM, respectively), whereas trans complexes 2 and 4 are more active than trans-DDP (mean IC₅₀ = 10.6, 26, and 164 μM, respectively), thus indicating that substitution of acetonimine for one or two ammine ligands determines strikingly different effects depending upon the complex geometry.