School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
School of Pharmacy, Nantong University, Nantong, Jiangsu, China.
Eur J Med Chem. 2017 Jul 7;134:207-217. doi: 10.1016/j.ejmech.2017.04.026. Epub 2017 Apr 12.
We synthesized two mixed-ligand Cu(II) complexes containing different aroylhydrazone ligands and a pyridine co-ligand, namely, [Cu(L1)(Py)] (C1) and [Cu(L2)(Py)(Br)] (C2) (L1 = (E)-2-hydroxy-N'-((2-hydroxynaphthalen-1-yl)methylene)benzohydrazide, Py = pyridine, L2 = (E)-2-hydroxy-N'-(phenyl(pyridin-2-yl)methylene)benzohydrazide), and assessed their chemical and biological properties to understand their marked activity. C2 showed better anticancer activity than C1 in various human cancer cell lines, including the cisplatin-resistant lung cancer cell line A549cisR. Both Cu(II) complexes, especially C2, displayed promising anti-metastatic activity against HepG2 cells. Spectroscopic titration and agarose gel electrophoresis experiments indicated that C2 exhibited binding affinity toward calf-thymus DNA and efficient pBR322 DNA-cleaving ability. Further mechanistic studies showed that C2 effectively induced DNA damage and thus led to cell cycle arrest at the G2/M phase, and also stimulated mitochondrial dysfunction mediated by reactive oxygen species and caspase-dependent apoptosis.
我们合成了两种含有不同酰腙配体和吡啶辅助配体的混合配体 Cu(II) 配合物，即 [Cu(L1)(Py)]（C1）和[Cu(L2)(Py)(Br)]（C2）（L1 = (E)-2-羟基-N'-((2-羟基萘-1-基)亚甲基)苯甲酰肼，Py = 吡啶，L2 = (E)-2-羟基-N'-(苯基(吡啶-2-基)亚甲基)苯甲酰肼），并评估了它们的化学和生物学性质，以了解它们的显著活性。C2 在各种人类癌细胞系中表现出比 C1 更好的抗癌活性，包括顺铂耐药的肺癌细胞系 A549cisR。两种 Cu(II) 配合物，尤其是 C2，对 HepG2 细胞表现出有前途的抗转移活性。光谱滴定和琼脂糖凝胶电泳实验表明，C2 对小牛胸腺 DNA 具有结合亲和力和有效的 pBR322 DNA 切割能力。进一步的机制研究表明，C2 有效诱导 DNA 损伤，从而导致细胞周期停滞在 G2/M 期，并通过活性氧和 caspase 依赖性凋亡介导线粒体功能障碍。
