两种新型吡哆醛异烟酰腙氧钒(Ⅳ)配合物的合成及抗肿瘤活性研究  

Synthesis and Antitumor Activity of Two Novel Oxovanadium( Ⅳ) Complexes of Schiff Base and Pyridoxal Isonicotinoyl Hydrazone

作　　者：付强强 张咏莉 唐敬 陆家政 FU Qiang-qiang;ZHANG Yortg-li;TANG Jing;LU Jia-zheng(School of Pharmacy;School of Basic Courses,Guangdong Pharmaceutical University,Guangzhou 510006,China)

机构地区：[1]广东药科大学药学院,广东广州510006 [2]广东药科大学基础学院,广东广州510006

出　　处：《化学试剂》2018年第11期1026-1031,共6页Chemical Reagents

基　　金：广东省科技计划项目(2013B031800018);广东药科大学科技处与附属医院联合基金资助项目(2014-36)

摘　　要：设计合成了两种含吡哆醛异烟酰腙Schiff碱配体的新型氧钒（Ⅳ）配合物[VO（PIH）（FPIP）]（PIH=吡哆醛异烟酰腙,FPIP=2-（4-氟苯基）咪唑[4,5-f][1,10]菲啰啉）和[VO（PIH）（ClPIP）]（ClPIP=2-（4-氯苯基）咪唑[4,5-f][1,10]菲啰啉）,通过元素分析、IR、ESI-MS和1HNMR等方法表征其结构。采用MTT法检测配合物对人肝癌细胞株（HepG2）、人肺癌细胞株（A549）及人宫颈癌细胞株（Hela）的抑制作用。结果显示,这两种配合物对HepG2、A549和Hela细胞的生长均具有较强的抑制作用,其中对Hela细胞的抑制作用最明显。此外,采用流式细胞术和荧光显微镜对抑制机理进行初步探讨。实验表明,这两种配合物都可诱导肿瘤细胞发生凋亡,阻滞肿瘤细胞分裂周期均停滞在G0/G1期。这两种配合物都使肿瘤细胞的活性氧水平升高,线粒体膜电位降低,提示这些配合物可能是通过ROS介导的,并伴随着线粒体功能障碍途径诱导细胞发生凋亡。Two novel oxovanadium（ Ⅳ） complexes [VO（ PIH）（ FPIP） ]（ PIH = pyridoxal isonicotinoyl hydrazone,FPIP = 2-（ 4-fluorine phenyl） imidazole [4,5-f][1,10]phenanthroline） and [VO（ PIH）（ ClPIP） ]（ ClPIP = 2-（ 4-Chlorine phenyl） imidazole[4,5-f][1,10]phenanthroline） containing Schiff base ligands containing pyridoxal isonicotinoyl hydrazone were synthesized and characterized by elemental analysis,IR,ESI-MS and 1 HNMR.The inhibitory effect of complexes on human hepatocellular carcinoma cell line（ HepG2）,human lung cancer cell line（ A549） and human cervical cancer cell line（ Hela） was detected by MTT assay.The results showed that these two complexes had strong inhibitory effects on the growth of HepG2,A549 and Hela cells,of which Hela cells had the most significant inhibitory effect. In addition,the inhibitory mechanism was preliminary investigated by flow cytometry and fluorescence microscopy.Experiments showed that these two complexes could induce apoptosis of tumor cells,blocking the cell cycle of tumor cells were arrested in the G0/G1 phase.All these two complexes increased the reactive oxygen species and decreased mitochondrial membrane potential in tumor cells,suggesting that these complexes may be mediated by ROS and apoptosis was induced along with mitochondrial dysfunction pathway.

关 键 词：吡哆醛异烟酰腙 氧钒配合物 抗肿瘤 细胞凋亡 

分 类 号：R914.3[医药卫生—药物化学]