title: Cytotoxicity profile of novel sterically hindered platinum(II) complexes with (1R,2R)-N(1),N(2)-dibutyl-1,2-diaminocyclohexane.
abstract: Four Pt(II) complexes of (1R,2R)-N(1),N(2)-dibutyl-1,2-diaminocyclohexane with two alkyl branches as steric hindrance have been designed and synthesized. In vitro cytotoxicity of these compounds indicated complex 4 is a cytotoxic agent more potent than its parent molecule, oxaliplatin, against almost all the tested cell lines. Agarose gel electrophoresis study showed that the kinetic reactivity of complex 4 with DNA is slow down due to the sterically hindered effect, demonstrating that it may possess a different mechanism of action from cisplatin. Flow cytometry results revealed that complex 4 induced apoptosis of tumor cells by blocking the cell-cycle progression in the G2/M phase. Western blot analysis showed it had a similar apoptotic mechanism to cisplatin which could induce apoptosis via a mitochondrial-dependent pathway.
authors: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors: Haiyan
authors: H
authors: Zhang
authors: 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: Shaohua
authors: S
authors: Gou
authors: Pharmaceutical Research Center and School of Chemistry and Chemical Engineering, Southeast University, Nanjing 211189, China.
authors: Jian
authors: J
authors: Zhao
authors: 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: Feihong
authors: F
authors: Chen
authors: 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: Gang
authors: G
authors: Xu
authors: Department of Science and Technology, Jiangsu Open University, Nanjing 210036, China.
authors: Xia
authors: X
authors: Liu
mesh_terms: D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D017209:Apoptosis / Q000187:drug effects; D002453:Cell Cycle / Q000187:drug effects; D045744:Cell Line, Tumor; D049109:Cell Proliferation / Q000187:drug effects; D003514:Cyclohexylamines / Q000737:chemistry / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D004354:Drug Screening Assays, Antitumor; D005434:Flow Cytometry; D006801:Humans; D015394:Molecular Structure; D009944:Organoplatinum Compounds / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: D000970:Antineoplastic Agents; D003514:Cyclohexylamines; C000606771:N(1),N(2)-dibutyl-1,2-diaminocyclohexane; D009944:Organoplatinum Compounds
keywords: Apoptotic mechanism; Platinum (II) complexes; Potent cytotoxicity; Steric hindrance