Crystal structure, cytotoxicity and action mechanism of Zn(II)/Mn(II) complexes with isoquinoline ligands
Crystal structure, cytotoxicity and action mechanism of Zn(II)/Mn(II) complexes with isoquinoline ligands
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异喹啉配体Zn(II)/Mn(II)配合物的晶体结构、细胞毒性及作用机制
DOI：
10.1016/j.jinorgbio.2017.01.001
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发表时间：
2017
影响因子：
3.9
通讯作者：
Hong Liang
中科院分区：
文献类型：
--
作者：
Feng-Yang Wang;Qian-Yu Xi;Ke-Bin Huang;Xiao-Ming Tang;Zhen-Feng Chen;Yan-Cheng Liu;Hong Liang
合成并表征了4个μ2-Cl桥联异喹啉双核金属配合物（MPDQ）2 Zn 2Cl 4（1）（MPDQ = 4.5-亚甲二氧基-1-吡啶二氢异喹啉），（PYP）2 Zn 2Cl 4（2）（PYP = 5-吡啶-2-基-[1，3]间二氧杂环戊烯[4，5-g]异喹啉），（MPDQ）2 Mn 2Cl 4（3），（PYP）2 Mn 2Cl 4（4）.所有配合物对多种癌细胞均表现出较强的增殖抑制活性。还阐明了它们引起癌细胞死亡的潜在分子机制。通过Annexin V+/PI−检测和DiD/DAPI染色试验证明复合物2诱导MGC-803细胞凋亡。进一步的研究表明，复合物2能够通过引发由活性氧的过量产生引起的DNA损伤来诱导癌细胞的内源性途径依赖性凋亡。基于这些研究，我们认为含异喹啉配体的Zn（II）配合物可以作为抗癌化疗药物的候选物。
Four μ2-Cl bridged dinuclear metal complexes with isoquinoline ligands, (MPDQ)2Zn2Cl4(1) (MPDQ = 4.5-methylenedioxy-1-pyridinedihydroisoquinoline), (PYP)2Zn2Cl4(2) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline), (MPDQ)2Mn2Cl4(3),and (PYP)2Mn2Cl4(4) were synthesized and characterized. All complexes exhibited strong proliferation inhibition activity against various cancer cells. The underlying molecular mechanisms through which they caused the cancer cell death were also elucidated. Induction of apoptosis in MGC-803 cells by complex2was evidenced by annexin V+/PI−detection and DiD/DAPI staining assay. Further investigation revealed that complex2was able to induce intrinsic pathway-dependent apoptosis in cancer cells by triggering DNA damage which was caused by the overproduction of reactive oxygen species. Based on these studies, we suggest that Zn(II) complexes containing isoquinoline ligands can be developed as candidates foranti-cancer chemotherapeutics.