一种多吡啶双核单功能铂配合物的合成、晶体结构及抗癌活性  

Synthesis,crystal structure,and anticancer activity of a polypyridyl binuclear monofunctional platinum(Ⅱ)complex

作　　者：李训一 王宇静 周子默 方霄 汪清清 胡美纯 杨晓松 王小波[1] LI Xun-Yi;WANG Yu-Jing;ZHOU Zi-Mo;FANG Xiao;WANG Qing-Qing;HU Mei-Chun;YANG Xiao-Song;WANG Xiao-Bo(School of Pharmacy,Medical Department,Hubei University of Science and Technology,Xianning,Hubei 437100,China;Hubei Key Laboratory of Diabetes and Angiopathy,Hubei University of Science and Technology,Xianning,Hubei 437100,China;School of Basic Medical Sciences,Medical Department,Hubei University of Science and Technology,Xianning,Hubei 437100,China)

机构地区：[1]湖北科技学院医学部药学院,咸宁437100 [2]湖北科技学院医学部,糖尿病心脑血管病变湖北省重点实验室,咸宁437100 [3]湖北科技学院医学部基础医学院,咸宁437100

出　　处：《无机化学学报》2023年第1期141-149,共9页Chinese Journal of Inorganic Chemistry

基　　金：湖北省教育厅重点项目(No.D20212802);湖北省自然科学基金(No.2021CFB439);湖北省卫健委项目(No.WJ2019Q022)资助。

摘　　要：合成了一种含有多吡啶基配体2,6-双((双(吡啶-2-基甲基)氨基)甲基)吡啶(BPA-TPA)的双核单功能铂(Ⅱ)配合物[Pt_(2)(BPA-TPA)Cl_(2)]Cl_(2)(Pt_(2)-BPA-TPA),以核磁共振波谱和高分辨质谱进行表征,并通过X射线单晶衍射确定了Pt_(2)-BPA-TPA的结构。琼脂凝胶电泳实验表明Pt_(2)-BPA-TPA在10μmol·L^(-1)的低浓度下可有效切割pBR322 DNA。通过CCK-8(cell counting kit-8)实验检测了Pt_(2)-BPA-TPA对人肺癌细胞系A549的细胞毒性,结果显示Pt_(2)-BPA-TPA表现出比顺铂更好的抗癌活性,其主要通过触发DNA损伤和上调下游凋亡相关细胞信号通路蛋白(p21蛋白和cleaved-caspase-3)诱导细胞凋亡。A binuclear monofunctional platinum(Ⅱ)complex,[Pt_(2)(BPA-TPA)Cl_(2)]Cl_(2)(Pt_(2)-BPA-TPA),containing polypyridyl ligand 2,6-bis((bis(pyridin-2-ylmethyl)amino)methyl)pyridine was synthesized and characterized by nuclear magnetic resonance and high-resolution mass spectroscopy.In addition,the structure of Pt_(2)-BPA-TPA was determined by X-ray single-crystal diffraction.Agarose gel electrophoresis experiments were used to demonstrate the efficient pBR322 DNA-cleaving activity of Pt_(2)-BPA-TPA at a low concentration of 10μmol·L^(-1).In CCK-8(cell counting kit-8)cytotoxicity studies using the A549 human lung cancer cell line,Pt_(2)-BPA-TPA demonstrated enhanced anticancer activity compared with cisplatin.Mechanistic studies provided evidence that Pt_(2)-BPA-TPA induces apoptosis via triggering DNA damage and upregulating downstream cellular signaling cascades of p21 and cleaved-caspase-3.CCDC:2115372.

关 键 词：单功能铂 抗癌活性 DNA切割 双核配合物 晶体结构 

分 类 号：O614.826[理学—无机化学]