Methyl Benzoate Gallium(III) corrole complexes: DNA-binding, Photocleavage Activity, Cytotoxicity on Tumor Cells

Methyl Benzoate Gallium(III) corrole complexes: DNA-binding, Photocleavage Activity, Cytotoxicity on Tumor Cells
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苯甲酸甲酯镓 (III) 咔咯络合物:DNA 结合、光裂解活性、对肿瘤细胞的细胞毒性

DOI:
10.1002/aoc.3571
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发表时间:
2017-03
影响因子:
3.9
通讯作者:
Liu Hai-Yang
Liu Hai-Yang
中科院分区:
化学3区
文献类型:
--
作者:
Wang Jia-Min;Li Yuan;Yuan Hui-Qing;Wu Dan-Hong;Ying Xiao;Shi Lei;Zhang Hai-Tao;Liu Hai-Yang

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合成并表征了两种新的镓咔咯配合物10-(4-甲氧羰基苯基)-5,15-双(五氟苯基)咔咯镓(III)(1-Ga)和5,15-双(4-甲氧羰基苯基)-10-(五氟苯基)咔咯镓(III)(2-Ga)。用荧光法、紫外-可见光谱法、粘度法、分子对接法和琼脂糖凝胶电泳法研究了这些配合物与CT-DNA的相互作用。结果表明,1-Ga和2-Ga均能通过大沟结合与DNA发生作用,并能有效地切割超螺旋质粒DNA。抑制剂和单线态氧测试表明,单线态氧是参与1-Ga或2-Ga引发的光切割DNA的活性氧物种。细胞活力实验表明,1-Ga和2-Ga对所测试的QGY-7701和MHCC-H/L肿瘤细胞系显示出高的光毒性和低的暗毒性。荧光探针实验表明,肿瘤细胞吸收的1-Ga和2-Ga主要定位于线粒体,照射后线粒体膜电位发生了改变。
Two new gallium corrole complexes, 10-(4-Methoxycarbonylphenyl) -5, 15-bis(pentafluorophenyl)corrolatogallium(III)(1-Ga) and 5,15-bis(4-Methoxycarbonylphenyl)-10-(pentafluorophenyl)corrolatogallium(III)(2-Ga), were synthesized and characterized. The interaction of these gallium corrole complexes with CT-DNA was studied by fluorescence methods, UV–visible, viscosity measurements, molecular docking as well as agarose gel electrophoresis. The results revealed that both 1-Ga and 2-Ga interact with DNA via major groove binding and could cleavage the supercoiled plasmid DNA efficiently under irradiation. The inhibitor and singlet oxygen test indicated that singlet oxygen was the reactive oxygen species involved in the photocleavage DNA initiated by 1-Ga or 2-Ga. Cell viability experiments indicated that 1-Ga and 2-Ga show high photocytotoxicity and low dark toxicity towards tested QGY-7701 and MHCC-H/L tumor cell lines. Fluorescence probe tests showed the absorbed 1-Ga and 2-Ga in tumor cells are mainly localized in mitochondria, and the mitochondria membrane potential disruption was observed after irradiation.
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