Isoquinoline derivatives Zn(II)/Ni(II) complexes: Crystal structures, cytotoxicity, and their action mechanism
Isoquinoline derivatives Zn(II)/Ni(II) complexes: Crystal structures, cytotoxicity, and their action mechanism
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异喹啉衍生物 Zn(II)/Ni(II) 配合物：晶体结构、细胞毒性及其作用机制
DOI：
10.1016/j.ejmech.2015.05.038
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发表时间：
2015
影响因子：
6.7
通讯作者：
Hong Liang
中科院分区：
文献类型：
--
作者：
Ke-Bin Huang;Hui-Yan Mo;Zhen-Feng Chen;Jian-Hua Wei;Yan-Cheng Liu;Hong Liang
合成了三种异喹啉衍生物的过渡金属配合物：[（MPDQ）2 Zn（C2 H5 OH）ClO 4] ClO 4（1）（MPDQ = 4，5-亚甲二氧基-1-吡啶二氢异喹啉），[（PYP）2 Zn（H2O）]（ClO 4）2（2）（PYP = 5-吡啶-2-基-[1，3]间二氧杂环戊烯[4，5-g]异喹啉）和[（MPDQ）2Ni（CH 3OH）ClO 4] ClO 4（3）。所有配合物均表现出较强的抑制肿瘤细胞增殖的活性，对肿瘤细胞和正常细胞具有高度的选择性。BEL-7404细胞对复合物2最敏感，诱导细胞凋亡。该过程涉及线粒体膜电位去极化、PARP蛋白裂解、Bcl-2、p53、p21表达及caspase家族成员的激活。考虑到这些发现，可以提出复合物2通过线粒体途径诱导癌细胞凋亡。通过荧光光谱、圆二色谱和粘度法研究了配合物2与DNA的相互作用，结果表明配合物2与DNA的相互作用主要是通过嵌入方式进行的。
Three transition metal complexes with isoquinoline derivatives: [(MPDQ)2Zn(C2H5OH)ClO4]ClO4(1) (MPDQ = 4,5-methylenedioxy-1-pyridinedihydroisoquinoline), [(PYP)2Zn(H2O)](ClO4)2(2) (PYP = 5-pyridin-2-yl-[1,3]dioxolo[4,5-g]isoquinoline) and [(MPDQ)2Ni(CH3OH)ClO4]ClO4(3) were synthesized and fully characterized. All complexes exhibited strong proliferation inhibition activity against various tested cancer cells with high selectivity to tumour and normal cells. BEL-7404 cells were found most sensitive to complex2by inducing apoptosis. The process involved the mitochondrial membrane potential depolarization, PARP-proteins cleavage, Bcl-2, p53, p21 expression and caspase family members' activation. Taking these findings into account, it can propose that complex2induce cancer cell apoptosisviamitochondrial pathways. The interaction of complex2with DNA investigated by fluorescence, CD and viscosity indicated that complex2interact with DNA mainlyviaintercalation.