Cytotoxicity profile of novel sterically hindered platinum(II) complexes with (1R,2R)-N1,N2-dibutyl-1,2-diaminocyclohexane

Four Pt(II) complexes of (1R,2R)-N-1,N-2-dibutyl-1,2-diaminocyclohexane with two alkyl branches as steric hindrance have been designed and synthesized. In vitro cytotoxicity of these compounds indicated complex 4 is a cytotoxic agent more potent than its parent molecule, oxaliplatin, against almost all the tested cell lines. Agarose gel electrophoresis study showed that the kinetic reactivity of complex 4 with DNA is slow down due to the sterically hindered effect, demonstrating that it may possess a different mechanism of action from cisplatin. Flow cytometry results revealed that complex 4 induced apoptosis of tumor cells by blocking the cell-cycle progression in the G2/M phase. Western blot analysis showed it had a similar apoptotic mechanism to cisplatin which could induce apoptosis via a mitochondrial-dependent pathway. (C) 2015 Elsevier Masson SAS. All rights reserved.