title: Two New Mononuclear Copper(II)-Dipeptide Complexes of 2-(2'-Pyridyl)Benzoxazole: DNA Interaction, Antioxidation and in Vitro Cytotoxicity Studies.
abstract: Two new mononuclear mixed ligand copper(II) complexes [Cu(PBO)(Gly-gly)(H2O)]·ClO4·1.5H2O (1) and [Cu(PBO)(Gly-L-leu)(H2O)]·ClO4(2) (PBO is 2-(2'-pyridyl)benzoxazole, Gly-gly and Gly-L-leu are Glycyl-glycine anion and Glycyl-L-leucine anion, respectively), have been prepared and characterized by various analytical and spectral techniques. The interactions of the complexes with DNA were investigated using multi-spectroscopic methods (absorption, emission, circular dichroism), viscometry and electrochemical titration as well as molecular docking technique. The results indicated that 1 and 2 are bound to calf thymus DNA (CT-DNA) through an intercalative mode. The thermodynamic analyses revealed that the reactions between the Cu(II) complexes with DNA are spontaneous with negative Gibbs free energy (ΔG). The positive changes of enthalpy (ΔH) and entropy (ΔS) suggested that the binding processes are dominated by hydrophobic interaction accompanying with endothermic. Also, the complexes exhibited efficient oxidative cleavage of pBR322 plasmid DNA in the presence of ascorbic acid, probably induced by •OH as reactive oxygen species. In addition, 1 and 2 displayed excellent antioxidant activities with the IC50values of 0.112 and 0.191 μM, respectively, using the mean of nitroblue tetrazolium (NBT) photochemical reduction under a nonenzymatic condition. Moreover, the complexes were screened for their in vitro cytotoxicity against three human carcinoma cell lines (HeLa, PC-3 and A549), in which 2 owns higher cytotoxicity, which was consistent with DNA binding and cleavage ability order of the complexes. This results showed the in vitro biochemical potentials of the Cu(II)-dipeptide complexes with aromatic heterocyclic, viz. effective metallopeptide-nucleases, SOD mimics and non-platinum chemotherapeutic metallopharmaceuticals and their structure-activity relationship, which may contribute to the rational molecular design of new metallopeptide based chemotherapeutic agents.
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Qian
authors.initials: Q
authors.lastname: Gan
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Yongyu
authors.initials: Y
authors.lastname: Qi
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Yahong
authors.initials: Y
authors.lastname: Xiong
authors.affiliation: Department of Applied Mathematics, South China Agricultural University, Guangzhou, 510642, People's Republic of China.
authors.forename: Yinlian
authors.initials: Y
authors.lastname: Fu
authors.affiliation: Department of Applied Chemistry, South China Agricultural University, Guangzhou, 510642, People's Republic of China. lexy@scau.edu.cn.
authors.forename: Xueyi
authors.initials: X
authors.lastname: Le
mesh_terms: D000818:Animals; D000970:Antineoplastic Agents / Q000737:chemistry / Q000494:pharmacology*; D000975:Antioxidants / Q000737:chemistry / Q000494:pharmacology*; D001583:Benzoxazoles / Q000737:chemistry; D002417:Cattle; D049109:Cell Proliferation / Q000187:drug effects*; D056831:Coordination Complexes / Q000737:chemistry / Q000494:pharmacology*; D003300:Copper / Q000737:chemistry*; D004247:DNA / Q000378:metabolism*; D004151:Dipeptides / Q000737:chemistry; D006801:Humans; D007364:Intercalating Agents / Q000737:chemistry / Q000494:pharmacology*; D062105:Molecular Docking Simulation; D014407:Tumor Cells, Cultured
chemical_list: D000970:Antineoplastic Agents; D000975:Antioxidants; D001583:Benzoxazoles; D056831:Coordination Complexes; D004151:Dipeptides; D007364:Intercalating Agents; D003300:Copper; D004247:DNA; C427203:calf thymus DNA
keywords: Antioxidation; Cu(II)-dipeptide complexes; Cytotoxicity; DNA interaction; Fluorescence quenching; Molecular docking