title: A monofunctional trinuclear platinum complex with steric hindrance demonstrates strong cytotoxicity against tumor cells.
abstract: Polynuclear platinum complexes constitute a special class of hopeful antitumor agents. In this study, a Y-type monofunctional trinuclear platinum complex (MTPC) with 1,3,5-tris(pyridin-2-ylmethoxy)benzene, ammine and chloride as ligands was synthesized and characterized by (1)H NMR and electrospray ionization mass spectrometry (ESI-MS). The DNA binding mode of MTPC was investigated using circular dichroism spectroscopy and gel electrophoresis, and the reactivity of MTPC towards glutathione was studied by (1)H NMR and ESI-MS. The results show that MTPC can affect the conformation of calf-thymus DNA (CT-DNA) significantly and tends to form 1,4-GG rather than 1,2-GG intrastrand crosslinks, which are different from the instance of cisplatin. MTPC reacts with glutathione quite slowly in comparison with cisplatin because of the steric hindrance. The cytotoxicity of MTPC was tested on the human breast cancer cell line MCF-7, the human non-small-cell lung cancer cell line A549, and the human ovarian cancer cell line Skov-3 by the MTT [3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide] assay. MTPC is more potent than or comparable to cisplatin. The cellular inhibition mode of MTPC was examined by flow cytometry using MCF-7 cells. MTPC arrests the cell cycle mainly in G2 or M phase, while cisplatin arrests the cell cycle in S phase. Similar to cisplatin, MTPC kills the cells predominantly through an apoptotic pathway.
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Shangnong
authors.initials: S
authors.lastname: Wu
authors.affiliation: State Key Laboratory of Pharmaceutical Biotechnology, School of Life Sciences, Nanjing University, Nanjing 210093, PR China; State Key Laboratory of Analytical Chemistry for Life Science, Nanjing University, Nanjing 210093, PR China. Electronic address: boxwxy@nju.edu.cn.
authors.forename: Xiaoyong
authors.initials: X
authors.lastname: Wang
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Yafeng
authors.initials: Y
authors.lastname: He
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Zhenzhu
authors.initials: Z
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China.
authors.forename: Chengcheng
authors.initials: C
authors.lastname: Zhu
authors.affiliation: State Key Laboratory of Coordination Chemistry, School of Chemistry and Chemical Engineering, Nanjing University, Nanjing 210093, PR China. Electronic address: zguo@nju.edu.cn.
authors.forename: Zijian
authors.initials: Z
authors.lastname: Guo
mesh_terms: D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis; D001483:Base Sequence; D059447:Cell Cycle Checkpoints; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D004247:DNA / Q000737:chemistry; D005978:Glutathione / Q000737:chemistry; D006801:Humans; D061986:MCF-7 Cells; D010984:Platinum / Q000737:chemistry; D017671:Platinum Compounds / Q000737:chemistry / Q000494:pharmacology*
chemical_list: D000970:Antineoplastic Agents; D056831:Coordination Complexes; D017671:Platinum Compounds; D010984:Platinum; D004247:DNA; C427203:calf thymus DNA; D005978:Glutathione
keywords: Antitumor drug; Apoptosis; DNA binding; Glutathione; Polynuclear platinum complex