title: Synthesis and structure of new dicopper(II) complexes bridged by N-(2-hydroxy-5-methylphenyl)-N'-[3-(dimethylamino)propyl]oxamide with in vitro anticancer activity: A comparative study of reactivities towards DNA/protein by molecular docking and experimental assays.
abstract: Two new dicopper(II) complexes bridged by N-(2-hydroxy-5-methylphenyl)-N'-[3-(dimethyl-amino)propyl]oxamide (H3hmpoxd), and end-capped with 4,4'-dimethyl-2,2'-bipyridine (Me2bpy) and 2,2'-bipyridine (bpy), were synthesized and structurally characterized, namely [Cu2(hmpoxd)(CH3OH)(Me2bpy)](ClO4) (1) and [Cu2(hmpoxd)(bpy)](ClO4)∙CH3OH (2). The single-crystal X-ray diffraction analysis reveals that the endo- and exo-copper (II) ions bridged by the cis-hmpoxd(3-) ligand are located in square-planar and square-pyramidal geometries, respectively, for 1, and square-planar environments in 2. The DNA/protein-binding natures are studied theoretically and experimentally, indicating that both the two complexes can interact with the DNA in the mode of intercalation, and effectively quench the intrinsic fluorescence of protein BSA via the favored binding sites Trp213 for 1 and Trp134 for 2. In vitro anticancer activities showed that the two complexes are active against the selected tumor cell lines, and the anticancer activities are consistent with their DNA/BSA-binding affinities following the order of 1 > 2. The synergistic hydrophobicity of the bridging and terminal ligands in these complexes on DNA/BSA-binding events and in vitro anticancer activities is preliminarily discussed.
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China.
authors.forename: Kang
authors.initials: K
authors.lastname: Zheng
authors.affiliation: Qingdao Municipal Medical Group, Qingdao 266011, Shandong, PR China.
authors.forename: Mei-Xing
authors.initials: MX
authors.lastname: Yan
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China. Electronic address: yantuanli@ouc.edu.cn.
authors.forename: Yan-Tuan
authors.initials: YT
authors.lastname: Li
authors.affiliation: School of Medicine and Pharmacy, Ocean University of China, Qingdao 266003, PR China.
authors.forename: Zhi-Yong
authors.initials: ZY
authors.lastname: Wu
authors.affiliation: College of Marine Life Science, Ocean University of China, Qingdao 266003, PR China. Electronic address: cuiweiyan@ouc.edu.cn.
authors.forename: Cui-Wei
authors.initials: CW
authors.lastname: Yan
mesh_terms: D000577:Amides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D001665:Binding Sites; D002417:Cattle; D045744:Cell Line, Tumor; D056831:Coordination Complexes / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry* / Q000494:pharmacology*; D018360:Crystallography, X-Ray; D004247:DNA / Q000378:metabolism; D006801:Humans; D007364:Intercalating Agents / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D008024:Ligands; D062105:Molecular Docking Simulation; D009369:Neoplasms / Q000188:drug therapy / Q000378:metabolism; D011725:Pyridines / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D012710:Serum Albumin, Bovine / Q000378:metabolism
chemical_list: C560551:4,4'-dimethyl-2,2'-bipyridine; D000577:Amides; D000970:Antineoplastic Agents; D056831:Coordination Complexes; D007364:Intercalating Agents; D008024:Ligands; D011725:Pyridines; D012710:Serum Albumin, Bovine; D003300:Copper; D004247:DNA
keywords: Cytotoxicity; DNA/Protein-binding property; Molecular docking; Structure elucidation; Synergistic hydrophobicity; μ-Oxamido-bridged dicopper(II) complexes