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)-N1-2-butyl-1,2-diaminocyclohexane-N,N′] dichloroplatinum(II), was much more active in vitro (IC50 = 1.82 μM) 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.

Graphical abstractNine platinum(II) complexes with N-monoalkyl 1R,2R-diaminocyclohexane as ligands were synthesized, characterized and evaluated for their in vitro antitumor activities against four cancer cell lines. The mechanism of cellular death and interaction with DNA were also studied.Figure optionsDownload full-size imageDownload as PowerPoint slideHighlights► Pt(II) complexes with a series of N-monoalkyl 1R,2R-diaminocyclohexane ligands. ► All compounds showed cytotoxicity against A549 comparable to cisplatin and oxaliplatin. ► Linear butyl substituents had an important effect on the cytotoxicity of complexes. ► Compounds induced apoptosis analogous to cisplatin. ► Compounds produced DNA fragmentation and distortion.