Synthesis, cytotoxicity, and DNA-binding levels of ammine/cyclohexylamine platinum(II) complexes with dicarboxylates

Four new ammine/cyclohexylamine platinum(II) complexes with dicarboxylates (a-d) have been synthesized and characterized by elemental analysis, conductivity, IR, UV, and (HNMR)-H-1 spectra techniques. The cytotoxicity of the complexes was tested by MTT assay. The cell cycle analysis and the levels of total platinum bound to DNA were measured by flow cytometry and ICP-MS. The results show that the cytotoxicity of complexes (a-d) against EJ, HCT-8, BGC-823, HL-60, and MCF-7 cell lines decreases in the sequence: b>a>c>d. Complexes (a-d) have better cytotoxicity against EJ and HL-60 and complex (b) demonstrates cytotoxicity superior to that of the clinically established cisplatin. The complexes (a-d) induced a concentration-dependent accumulation of HL-60 cells in the G(2)/M phase of the cell cycle as cisplatin. The levels of total platinum bound to DNA in HL-60 and EJ cells decrease in the sequence: b>cisplatin>a>c>d under the same experimental conditions.