Antitumor platinum(II) complexes of N-monoalkyl 1R,2R-diaminocyclohexanes with 3-(nitrooxy)cyclobutane-1,1-dicarboxylate as a leaving group

作者：Zhao Jian; Gou Shaohua^*; Xu Gang; Cheng Lin

来源：European Journal of Medicinal Chemistry, 2014, 85: 408-417.

DOI：10.1016/j.ejmech.2014.08.007

• NO-donor
• Anticancer
• Platinum complex

A series of platinum(II) complexes of N-monoalkyl-1R,2R-diaminocylclohexanes with 3-(nitrooxy) cyclobutane-1,1-dicarboxylate as a leaving group were synthesized and characterized by elemental analysis, IR, H-1, C-13 and Pt-195 NMR spectroscopy together with ESI-MS spectrometer. In vitro cytotoxicity study on these complexes indicated they have considerable cytotoxicity against the tested cancer cell lines. Notably, complexes 2, 4, 6 and 8 showed high cytotoxicity against human A549 and HCT-116 cancer cell lines. The DNA binding of the platinum-based complexes 1 and 3-5 studied by agarose gel electrophoresis was in accordance with cytotoxicity to some extent. Reactions between the corresponding aqua analogues of the resulting complexes and glutathione (GSH) were studied by kinetics method under pseudo-first-order conditions using UV-Vis spectrophotometric technique. The results indicated that the introduction of alkyl moieties in 1R,2R-diaminocyclohexane (1R,2R-DACH) decreased the reaction rates of the aqua analogues of complexes 3-5 and GSH under the tested condition. Moreover, the stability of complex 8 was investigated by HPLC MS technique at different time in 36 h.

• 出版日期2014-10-6
• 单位东南大学