Synthesis and in vitro antitumoral activity of novel O,O '-di-2-alkyl-(S,S)-ethylenediamine-N,N '-di-2-propanoate ligands and corresponding platinum(II/IV) complexes

Syntheses of two novel ligand precursors O,O'-diisopropyl- (1a) and O,O'-diisobutyl-(S,S)-ethylenediamine-N,N'-di-2-propanoate dihydrochloride monohydrate (1b) and the corresponding dichloroplatinum(II) (2a and 2b) and tetrachloroplatinum(IV) complexes (3a and 3b) are described here. The substances were characterized by IR, H-1 and C-13 spectroscopy and elemental analysis. Crystal structures were determined for la and the corresponding platinum(IV) complex, 3a. In vitro antiproliferative activity was determined against tumor cell lines: human adenocarcinoma HeLa, human myelogenous leukemia K562, human malignant melanoma Fem-x, rested and stimulated normal immunocompetent cells (human peripheral blood mononuclear PBMC cells) using KBR test (Kenacid Blue Dye binding test). The IC50(mu M) values for the most active compound 3a were: 30.48 +/- 2.54; 12.26 +/- 2.60; 13.68 +/- 3.22; 80.18 +/- 24.07 and 71.30 +/- 21.70, respectively. (C) 2008 Elsevier Inc. All rights reserved