Synthesis, characterization and in vitro antitumour activity of a series of novel platinum(II) complexes bearing Schiff base ligands

A series was neutral platinum(II) complexes bearing OCH3- or F-substituted 3,4-bis(4-fluorophenyl)-1,6-bis(2-hydroxyphenyl)-2,5-diazahexa-1,5-dienes (diarylsalenes) were synthesized and tested for in vitro antitumour activity. The growth inhibitory effects depended on the configuration and the substitution pattern of the salicylidene moiety. The lead compound [meso-3,4-bis(4-fluorophenyl)-1,6-bis(2-hydroxyphenyl)-2,5-diazahexa-1,5-diene]platinum(II) (1-Pt) reduced the cell growth of MCF-7 (IC50 = 7.6 mu M) and MDA-MB 231 cells (IC50 = 10.0 mu M), but was inactive against HT-29 cells at the used concentration range (IC50 > 20 mu M). The change of the configuration (meso -> d,l) at the 1,2-diimino-1,2-diarylethane bridge and methoxy substitution led to completely inactive compounds, while fluorine substituents increased the antiproliferative effects depending on their position (3-F < 5-F < 4-F < 6-F). Complex 10-Pt (6-F: IC50(MCF-7) = 1.5 mu M, IC50(MDA-MB 231) = 1.3 mu M, IC50 (HT-29) = 2.6 mu M) was as active as cisplatin (IC50(MCF-7) = 1.6 mu M, IC50(MDA-MB 231) = 1.5 mu M, IC50(HT-29) = 4.1 mu M). (C) 2012 Elsevier Masson SAS. All rights reserved.