Synthesis of two platinum(II) complexes with 2-methyl-8-quinolinol derivatives as ligands and study of their antitumor activities
Synthesis of two platinum(II) complexes with 2-methyl-8-quinolinol derivatives as ligands and study of their antitumor activities
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两种2-甲基-8-羟基喹啉衍生物为配体的铂(II)配合物的合成及其抗肿瘤活性研究
DOI：
10.1016/j.ejmech.2018.10.051
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发表时间：
2019
影响因子：
6.7
通讯作者：
Hong Liang
中科院分区：
文献类型：
--
作者：
Qi-Pin Qin;Shu-Long Wang;Ming-Xiong Tan;Yan-Cheng Liu;Ting Meng;Bi-Qun Zou;Hong Liang
合成并表征了两种铂（II）配合物[Pt（ClQ）（DMSO）Cl]（ClQ-Pt）和[Pt（BrQ）（DMSO）Cl]（BrQ-Pt），它们分别以5，7-二氯-2-甲基-8-羟基喹啉（H-ClQ）和5，7-二溴-2-甲基-8-羟基喹啉（H-BrQ）为配体。对ClQ-Pt和BrQ-Pt的单晶X-射线衍射表征以及其它光谱和分析研究表明，Pt（II）的配位几何构型可以描述为四配位的正方形平面几何构型。MTT法测定，ClQ-Pt对MGC 80 -3、T-24、Hep-G2和BEL-7402肿瘤细胞的IC_（50）值为5.02-34.38 μM。其中T-24细胞对ClQ-Pt和BrQ-Pt的敏感性最高，IC_（50）值分别为5.02 ± 0.62 μM和18.02 ± 1.05 μM。此外，ClQ-Pt引起更高百分比的凋亡T-24细胞（约100%）。33.75%）比BrQ-Pt（约. 23.85%）和顺铂（ca. 12.82%）。ClQ-Pt和BrQ-Pt可使T-24细胞周期阻滞于S期，细胞周期蛋白A（cyclin A）和细胞周期蛋白依赖性激酶2（CDK 2）表达水平下调。此外，ClQ-Pt和BrQ-Pt也引起线粒体功能障碍。有趣的是，ClQ-Pt的体外抗癌活性高于BrQ-Pt和顺铂，对T-24肿瘤细胞的选择性高于正常HL-7702细胞。综上所述，我们得出结论，5-和7-取代基团的ClQ配体起着重要的作用，在确定相应的Pt（II）配合物的抗增殖活性。
Two platinum(II) complexes, [Pt(ClQ)(DMSO)Cl] (ClQ-Pt) and [Pt(BrQ)(DMSO)Cl] (BrQ-Pt), with 5,7-dichloro-2-methyl-8-quinolinol (H-ClQ) and 5,7-dibromo-2-methyl-8-quinolinol (H-BrQ) as ligands, respectively, have been synthesized and characterized. The single-crystal X-ray diffraction characterization as well as other spectroscopic and analytical studies ofClQ-PtandBrQ-Ptrevealed that the coordination geometry of Pt(II) can be described as a four-coordinated square planar geometry. By MTT assay,ClQ-Ptdisplayed the most potent activity, with IC50values of 5.02–34.38 μM against MGC80-3, T-24, Hep-G2 and BEL-7402 tumor cells. Among them, the T-24 cells the highest sensitivity toClQ-PtandBrQ-Ptwith IC50value of 5.02 ± 0.62 μM and 18.02 ± 1.05 μM, respectively. In addition,ClQ-Ptcaused a higher percentage of apoptotic T-24 cells (ca. 33.75%) than that ofBrQ-Pt(ca. 23.85%) and cisplatin (ca. 12.82%). Mechanistic studies revealed thatClQ-PtandBrQ-Ptcaused T-24 cell cycle arrest at the S phase, as shown by the down-regulation of cyclin A and CDK2 expression levels. In addition,ClQ-PtandBrQ-Ptalso caused mitochondrial dysfunction. Interestingly, the in vitro anticancer activity ofClQ-Ptwas higher than those ofBrQ-Ptand cisplatin, more selective for T-24 tumor cells than for normal HL-7702 cells. Taken together, we concluded that the 5- and 7-substitution groups of the ClQ ligands play an important role in determining the anti-proliferation activity of the corresponding Pt(II) complexes.