title: Synthesis, in vitro cytotoxicity, and interaction with DNA of platinum(II) complexes with N-monocycloalkyl derivatives of 1R,2R-diaminocyclohexane as carrier ligands.
abstract: A series of platinum(II) complexes with N-monocyclopentyl/cyclohexyl derivatives of 1R,2R-diaminocyclohexane as carrier ligands and dicarboxylate anions as leaving groups were synthesized and characterized. All complexes were characterized by elemental analysis, IR, (1)H NMR, and (13)C NMR spectroscopy, as well as ESIMS. The in vitro antiproliferative activities were tested by MTT assay against four human cancer cell lines; breast carcinoma (MCF-7) and colon cancer (HCT-116) cells were particularly sensitive, especially to complexes 1f (IC(50) =9.81 and 1.49 μM) and 2f (IC(50) =4.59 and 0.36 μM). Flow cytometry indicated that representative compounds exert cytotoxicity toward MCF-7 and HCT-116 cells through induction of apoptosis and blockage of cell-cycle progression in the S phase, similar to cisplatin. The interaction between the platinum(II) complexes and pET22b plasmid DNA was observed by agarose gel electrophoresis, revealing that complex 2f has the capacity to distort plasmid DNA in a manner distinct from that of oxaliplatin.
authors.affiliation: Pharmaceutical Research Center, School of Chemistry and Chemical Engineering, Jiangsu Province High-Tech Key Laboratory for Biomedical Research, Southeast University, Nanjing 211189, China.
authors.forename: Yanyan
authors.initials: Y
authors.lastname: Sun
authors.forename: Shaohua
authors.initials: S
authors.lastname: Gou
authors.forename: Fei
authors.initials: F
authors.lastname: Liu
authors.forename: Runting
authors.initials: R
authors.lastname: Yin
authors.forename: Lei
authors.initials: L
authors.lastname: Fang
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry* / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D045744:Cell Line, Tumor; D003514:Cyclohexylamines / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D004354:Drug Screening Assays, Antitumor / Q000379:methods; D045325:HCT116 Cells; D006801:Humans; D008024:Ligands; D009682:Magnetic Resonance Spectroscopy; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000494:pharmacology; D000077150:Oxaliplatin; D010957:Plasmids / Q000235:genetics; D017671:Platinum Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D016196:S Phase / Q000187:drug effects
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; D008024:Ligands; D009944:Organoplatinum Compounds; D017671:Platinum Compounds; D000077150:Oxaliplatin; D004247:DNA; C030435:1,2-cyclohexanediamine