8-羟基喹啉衍生物锌(II)配合物的合成、结构及抗肿瘤活性  

Synthesis,Structure and Anticancer Activity of 8-Hydroxyquinoline Derivative′s Zinc(II)Complex

作　　者：张树琳 覃荣祝 黄燕珊 林啟福 韦祖壮 ZHANG Shulin;QIN Rongzhu;HUANG Yanshan;LIN Qifu;WEI Zuzhuang(College of Marine Sciences,Beibu Gulf University,Qinzhou 535011,China)

机构地区：[1]北部湾大学海洋学院,广西钦州535011

出　　处：《合成化学》2024年第12期1049-1055,共7页Chinese Journal of Synthetic Chemistry

基　　金：广西高校中青年教师科研基础能力提升项目(2024KY0448);高层次人才科研启动经费项目(23KYQD29);北部湾大学大学生创新训练项目(S202311607036)。

摘　　要：锌是生物体内必需的第二大微量元素,参与一系列的生理过程。以锌元素合成的金属配合物展示了抗肿瘤、抗菌、抗病毒和抗氧化等多种生理活性,对机体的维持和运转具有重要的调控功能。以8-羟基喹啉-2-甲醛(8-HQ)和2-肼基-4,6-二甲基嘧啶(H_(2)L)为起始原料,经缩合反应获得配体8-羟基喹啉衍生物希夫碱(8HQL)。以8HQL为活性配体,与ZnCl_(2)通过水热法合成8-羟基喹啉衍生物希夫碱-锌(II)配合物(8HQL-Zn)。X-单晶衍射结果表明:8HQL-Zn属斜方晶系,空间群为Pbca。运用密度泛函B3LYP方法对配合物8HQL-Zn进行量子化学计算,得到8HQL-Zn的前线轨道能量分布及能带间隙。运用MTT法对化合物进行抗肿瘤活性测试,结果表明:配合物8HQL-Zn对肿瘤细胞SW480和SY5Y的增殖具有明显抑制作用,其中,对SY5Y的抑制作用最强,IC_(50)=6.38±0.28μmol/L;对正常细胞LO2增殖的抑制作用相对较弱,IC_(50)=14.35±0.39μmol/L。肿瘤细胞选择性指数(SI)分析表明:配合物8HQL-Zn对癌细胞具有较好的选择性(SI=1.57~2.25)。Zinc plays a crucial role in a multitude of physiological processes as the second essential trace element in living organisms.The zinc-synthesized metal complexes exhibit diverse physiological activities and possess significant regulatory functions for maintaining and optimizing bodily functions,including antitumor,antibacterial,antiviral and antioxidant properties.In this study,the 8-hydroxyquinoline derivative(8HQL)was synthesized through a Schiff base condensation reaction using 8-hydroxyquinoline-2-carbaldehyde(8-HQ)and 2-hydrazino-4,6-dimethylpyrimidine(H_(2)L)as starting materials.By mixing the synthesized 8HQL with ZnCl_(2) and employing a hydrothermal method,a unique zinc(II)complex of the Schiff base derivative of 8-hydroxyquinoline,referred to as 8HQL-Zn,was successfully prepared.The structure of this Zn(II)complex was accurately characterized by X-ray single crystal diffraction analysis,revealing its belonging to the rhombic crystal system with a spatial group of Pbca.Using the B3LYP calculation method in density functional theory,quantum chemical calculations were performed on 8HQL-Zn complex to determine the frontier orbital energy distribution and band gap of 8HQL-Zn.MTT assay results demonstrated that 8HQL-Zn significantly inhibits the proliferation of SW480 and SY5Y tumor cells,particularly SY5Y,with an IC_(50) value of(6.38±0.28)μmol/L.This effect was more pronounced compared to normal LO2 cells which exhibited an IC_(50) value of(14.35±0.39)μmol/L.Furthermore,tumor cell selectivity index(SI)analysis revealed that 8HQL-Zn exhibits favorable selectivity towards cancer cells with a selectivity index ranging from 1.57 to 2.25.

关 键 词：8-羟基喹啉 锌(II)配合物 希夫碱 抗肿瘤活性 合成 

分 类 号：O614[理学—无机化学]