Fei Bao-Li, Yin Bin, Li Dong-Dong, Xu Wu-Shuang, Lu Yang
College of Chemical Engineering, Nanjing Forestry University, Nanjing, 210037, China.
State Key Laboratory of Coordination Chemistry, Coordination Chemistry Institute, Nanjing University, Nanjing, 210093, China.
J Biol Inorg Chem. 2016 Dec;21(8):987-996. doi: 10.1007/s00775-016-1394-3. Epub 2016 Sep 14.
To develop chiral anticancer drug candidates for molecular target DNA, the synthesis and characterization of a novel enantiomerically pure copper(II) complex [Cu 1 Cl ] (2) of an optically pure ligand N-(pyridin-2-ylmethylene) dehydroabietylamine (1) was carried out. The coordination geometry of the copper center is a distorted square-planar arrangement. The interactions of 1 and 2 with salmon sperm DNA were investigated by viscosity measurements, UV, fluorescence and circular dichroism (CD) spectroscopic techniques. All the results reveal that 1 and 2 interacted with DNA through intercalation and 2 exhibited a higher DNA binding ability. Further, 1 and 2 could cleave supercoiled pBR322 DNA by single strand and 2 displayed stronger cleavage ability in the presence of ascorbic acid. In vitro cytotoxicity of 1 and 2 against HeLa, SiHa, HepG-2 and A431 cancer cell lines was studied using CCK-8 assay. The results indicate that 2 had a superior cytotoxicity than 1 and the widely used drug cisplatin under identical conditions. Flow cytometry analysis demonstrates 2 produced death of HeLa cancer cells through an apoptotic pathway. Cell cycle analysis shows that 2 mainly arrested HeLa cells at the S phase. A novel enantiomerically pure copper(II) complex [Cu 1 Cl ] (2) of an optically pure ligand N-(pyridin-2-ylmethylene) dehydroabietylamine (1), based on natural product rosin has been synthesized. 2 has the potential to act as effective anticancer drug.
为了开发针对分子靶点DNA的手性抗癌候选药物，我们开展了一种新型对映体纯的铜（II）配合物[Cu 1 Cl ]（2）的合成与表征，该配合物由光学纯配体N-（吡啶-2-基亚甲基）脱氢枞胺（1）构成。铜中心的配位几何结构为扭曲的平面正方形排列。通过粘度测量、紫外、荧光和圆二色（CD）光谱技术研究了1和2与鲑鱼精DNA的相互作用。所有结果表明，1和2通过插入作用与DNA相互作用，且2表现出更高的DNA结合能力。此外，1和2可以通过单链切割超螺旋pBR322 DNA，并且在抗坏血酸存在的情况下，2表现出更强的切割能力。使用CCK-8法研究了1和2对HeLa、SiHa、HepG-2和A431癌细胞系的体外细胞毒性。结果表明，在相同条件下，2比1和广泛使用的药物顺铂具有更高的细胞毒性。流式细胞术分析表明，2通过凋亡途径导致HeLa癌细胞死亡。细胞周期分析表明，2主要将HeLa细胞阻滞在S期。基于天然产物松香的一种新型对映体纯的铜（II）配合物[Cu 1 Cl ]（2）已由光学纯配体N-（吡啶-2-基亚甲基）脱氢枞胺（1）合成。2有潜力作为有效的抗癌药物。
