Synthesis and in vitro antiproliferative activity of platinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane as ligands

Nine dichloridoplatinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane as ligands were synthesized and spectrally characterized. Among them, the crystal structure of a typical complex has been determined by X-Ray diffraction. All compounds were evaluated for their in vitro antitumor activity against four human cancer cell lines, which showed selective cytotoxicity comparable to that of positive agents against A549 (human non-small cell lung cancer) cell line. Especially complex 3, cis-[(1R,2R)-N-1-2-butyl-1,2-diaminocyclohexane-N,N'] dichloroplatinum(II), was much more active in vitro (IC50 = 1.82 mu M) than cisplatin against A549. The structure-activity relationship was summarized according to the cytotoxicity and QSAR properties. In addition, flow cytometry and agarose gel electrophoresis experiments were also applied to investigate the mode of action of the representative complexes. (C) 2012 Elsevier Masson SAS. All rights reserved.