Three structurally related Copper complexes with two isomers: DNA/BSA binding ability, DNA cleavage activity and excellent cytotoxicity

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• 作者：Dong-Yan Zhang^a ; ^c ; ¹ ; Yan Nie^b ; ¹ ; Hui Sang^b ; Jing-Jing Suo^a ; ^c ; Zong-Jin Li^b ; Wen Gu^a ; ^c ; Jin-Lei Tian^a ; ^c ; ^{tiant@nankai.edu.cn} ; Xin Liu^a ; ^c ; ^{liuxin64@nankai.edu.cn} ; Shi-Ping Yan^a ; ^c
• 关键词：Copper complexes ; DNA cleavage ; Anti-cancer ability ; ROS ; Caspase-3
• 刊名：Inorganica Chimica Acta
• 出版年：2017
• 出版时间：1 March 2017
• 年：2017
• 卷：457
• 期：Complete
• 页码：7-18
• 全文大小：2537 K
• 卷排序：457

文摘

Three Cu(II) complexes of [Cu(L1)(Br)2]·CH3CN (1), [Cu(L2)2(OAc)](PF6)·2C2H5OH (2), and [Cu(L1)(L2)](PF6)2 (3) (L1 = 2-(6-(pyridine-2-yl)-4-p-tolylpyridin-2-yl)pyridine, L2 = 2-(4-(pyridine-2-yl)-6-p  -tolylpyridin-2-yl)pyridine) were designed and synthesized as anti-cancer drugs. All complexes were structurally characterized by X-ray crystallography showing that three complexes were the mononuclear compounds with the triclinic crystal system p1¯ space group. The interaction between each of these three complexes and calf thymus DNA (CT-DNA) was investigated via spectroscopic techniques and viscosity measurement, which indicated that these complexes could bind to CT-DNA by intercalation. Moreover, DNA cleavage experiment showed that, in the natural light under an aerobic environment, all complexes could cleave DNA in the absence of exogenous oxidant agent, and that singlet oxygen (1O2) might serve as the major cleavage active species. Protein binding experiment indicated that 1–3 could bind to bovine serum albumin (BSA) with moderate bonding via the static quenching mechanism. In addition, the IC50 values of these three complexes were significantly lower which denoted highly anti-cancer activities in comparison to cisplatin. And each of these complexes could individually inhibit proliferation potential of cancer cells by promoting G1-phase cell cycle arrest (G1 arrest) and inducing apoptosis through the production of reactive oxygen species (ROS) and the activation of caspase-3