一个共配的铜基配合物的合成、晶体结构及抗肿瘤活性  

Synthesis, Single Crystal Structure and Anti-cancer Activity of A Novel Copper-based Complex Containing Co-ligands

作　　者：王雅楠 秦秀英[1] WANG Ya-nan;QIN Xiu-ying(College of Pharmacy,Guilin Medical University,Guilin 541004,China)

机构地区：[1]桂林医学院药学院,广西桂林541004

出　　处：《合成化学》2019年第11期883-889,共7页Chinese Journal of Synthetic Chemistry

基　　金：国家自然科学基金资助项目(21661011);广西自然科学基金资助项目(2016GXNSFAA380292)

摘　　要：合成了一个以N-{[2-羟基-4-甲氧基苯基]甲亚胺}苯丙氨酸阴离子和2,2′-联吡啶共配位的铜基配合物[Cu(C_(17)H_(15)NO_(4))(C_(10)H_(8)N_(2))]_(2)·CH_(3)OH(1),其结构经IR、元素分析、X-射线单晶衍射及Hirshfeld表面分析表征。用MTT法考察了配合物对耐顺铂的人肺癌细胞株(A549/DDP,DDP=顺铂)和人宫颈癌细胞株(C33A)的细胞毒性,用流式细胞术分析了配合物1诱导A549/DDP细胞凋亡和线粒体膜电位下降,初步考察了配合物1的抗肿瘤活性。结果表明:配合物1(CCDC:1913991)属于三斜晶系,Pī空间群,晶体学参数为:a=10.1770(5)A,b=10.2030(5)A,c=12.5857(6)A,α=104.576(4)°,β=101.518(4)°,γ=101.151(4)°,V=1197.71(11)3,Mr=1066.09,Z=1,R 1=0.0344,wR 2=0.0912,S=1.056;配合物1对肿瘤细胞有显著细胞毒性,对A549/DDP和C33A细胞作用24 h后,IC 50值分别为(9.75±0.39)μmol·L^(-1)和(28.13±1.27)μmol·L^(-1);其通过诱导A549/DDP细胞的线粒体膜电位下降而导致细胞凋亡,配合物1浓度为40.0μmol·L^(-1)时,与A549/DDP细胞孵育36 h,诱导A549/DDP细胞总凋亡率为41.0%,与A549/DDP细胞孵育30 h,使A549/DDP细胞的线粒体膜电位降低了47.4%。A copper-based complex,[Cu(C_(17)H_(15)NO_(4))(C_(10)H_(8)N_(2))]_(2)·CH_(3)OH(1),was synthesized by N-{[2-hydroxy-4-methoxyphenyl]methimide}phenylalanine anion and 2,2′-bipyridine as co-ligands.The crystal structure was characterized by IR,elemental analysis,X-ray single crystal diffraction and Hirshfeld surface analysis.The cytotoxicity of the complex against cisplatin-resistant human lung cancer cell line(A549/DDP,DDP=cisplatin)and human cervical cancer cell line(C33A)was investigated by a MTT assay.That the complex 1 induced the apoptosis of A549/DDP cells and the decrease of mitochondrial membrane potential was analyzed by flow cytometry,and the antitumor activity of the complex 1 was preliminarily investigated.Results showed that the complex 1(CCDC:1913991)belongs to triclinic crystal system,space group Pī,crystallographic parameters as follows:a=10.1770(5)A,b=10.2030(5)A,c=12.5857(6)A,α=104.576(4)°,β=101.518(4)°,γ=101.151(4)°,V=1197.71(11)3,Mr=1066.09,Z=1,R 1=0.0344,wR 2=0.0912,S=1.063.The complex 1 showed significant cytotoxicity against tumor cells.After cells were treated with the complex 1 for 24 hours,the IC 50 value for A549/DDP and C33A cells was(9.75±0.39)μmol·L^(-1) and(28.13±1.27)μmol·L^(-1),respectively.The complex 1 induced apoptosis by down-regulating the mitochondrial membrane potential of A549/DDP cells.After A549/DDP cells were incubated with the complex 1 for 36h,the complex 1(40.0μmol·L^(-1))induced the total apoptosis rate of A549/DDP cells to be 41.0%,and After A549/DDP cells were incubated with the complex 1 for 30h,the complex 1(40.0μmol·L^(-1))reduced the mitochondrial membrane potential by 47.4%.

关 键 词：N-{[2-羟基-4-甲氧基苯基]甲亚胺}苯丙氨酸 2 2′-联吡啶 铜基配合物 合成 晶体结构 抗肿瘤 

分 类 号：O614.1[理学—无机化学] O76[理学—化学]