title: Antitumor platinum(II) complexes of N-monoalkyl 1R,2R-diamino-cyclohexanes with 3-(nitrooxy)cyclobutane-1,1-dicarboxylate as a leaving group.
abstract: 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, (1)H, (13)C and (195)Pt 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.
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors.forename: Jian
authors.initials: J
authors.lastname: Zhao
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Southeast University, Nanjing 211189, China. Electronic address: sgou@seu.edu.cn.
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Southeast University, Nanjing 211189, China.
authors.forename: Gang
authors.initials: G
authors.lastname: Xu
authors.affiliation: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China; Jiangsu Province Hi-Tech Key Laboratory for Bio-medical Research, Southeast University, Nanjing 211189, China.
authors.forename: Lin
authors.initials: L
authors.lastname: Cheng
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D002264:Carboxylic Acids / Q000737:chemistry*; D045744:Cell Line, Tumor; D003510:Cyclohexanes / Q000737:chemistry*; D004278:DNA, Superhelical / Q000737:chemistry; D005260:Female; D005978:Glutathione / Q000378:metabolism; D006801:Humans; D008297:Male; D051379:Mice; D009569:Nitric Oxide / Q000378:metabolism; D009690:Nucleic Acid Conformation / Q000187:drug effects; D009944:Organoplatinum Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology* / Q000633:toxicity; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D002264:Carboxylic Acids; D003510:Cyclohexanes; D004278:DNA, Superhelical; D009944:Organoplatinum Compounds; D009569:Nitric Oxide; D005978:Glutathione
keywords: Anticancer; NO-donor; Platinum complex