CN105037402B - 一种1,2,4‑三唑类席夫碱锌配合物及其制备方法和应用 - Google Patents
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Abstract
本发明提供了一种席夫碱锌配合物及其制备方法和应用。本发明席夫碱锌配合物是5‑氯水杨醛缩‑3‑甲基‑4‑氨基‑5‑巯基‑1,2,4‑三唑席夫碱锌配合物。其制备方法：将5‑氯水杨醛缩‑3‑甲基‑4‑氨基‑5‑巯基‑1,2,4‑三唑席夫碱配体溶于甲醇或乙醇溶液中，向其中滴加等摩尔量的三乙胺，加热搅拌至配体完全溶解，将等摩尔量Zn(NO3)2·6H2O的甲醇或乙醇溶液滴加到上述反应溶液中，回流2～6个小时后，析出黄色固体产物。该固体粉末溶于二甲基亚砜，室温静置挥发，约4～6周后析出黄色块状晶体。本发明的配合物合成方法简单，结构稳定，晶体易得，活性实验表明，该配合物不仅能够有效抑制PTP1B活性，而且对乳腺癌细胞增殖也有一定的抑制作用，可在制备PTP1B抑制剂和抗肿瘤药物中应用。
Description
技术领域
本发明涉及三唑席夫碱锌配合物，具体涉及一种锌配合物及其制备方法和应用。
背景技术
最近研究表明蛋白酪氨酸磷酸酶(PTPs)是细胞信号传导途径中重要的调控因子，它和蛋白酪氨酸激酶共同调控细胞内的酪氨酸磷酸化水平，PTP催化活性的失常，会导致许多信号的传导失调，从而导致多种疾病包括恶性肿瘤的发生和发展，所以一些PTP已经成为抗肿瘤药物研究的新靶点，PTPs抑制剂也已经逐渐成为医药化学研究的一个重要课题。
目前国内外关于PTPs抑制剂的报道以有机小分子居多，而基于金属配合物的抑制剂研究才刚刚起步。众所周知，锌是重要的生命金属元素，并且有许多锌配合物被合成并且其抗癌活性已被测定，作为具有抗癌活性的金属配合物，与铂配合物相比，锌配合物具有更小的毒副作用，但是以蛋白酪氨酸磷酸酶1B(PTP1B)为作用靶点的锌配合物的各种生物活性研究的报道较少，所以一些结构新颖的锌配合物的设计合成及其对PTP1B活性抑制作用的研究对于开发基于锌配合物的抗肿瘤药物有重要的科学意义和应用价值。本发明涉及的三唑席夫碱锌配合物结构在国内外尚未见报道。
发明内容
本发明的目的在于提供一种三唑席夫碱锌配合物及其制备方法，以及该配合物在制备PTP1B抑制剂中的应用。
本发明提供的一种三唑席夫碱锌配合物，其结构式为：
本发明提供的一种三唑席夫碱锌配合物的制备方法，包括如下步骤：
(1)合成3-甲基-4-氨基-5-巯基-1,2,4-三唑(合成方法参照文献：化学试剂，2009，31(10)，785-788)；
(2)合成5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱配体(合成方法参照文献：化学试剂，2001，23(6)，344-345)；
(3)合成三唑席夫碱锌配合物：按每毫摩尔配体加入20～40mL甲醇或乙醇量，将5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱配体溶于甲醇或乙醇中，滴加等摩尔量的三乙胺，加热搅拌使配体完全溶解，然后将等摩尔量Zn(NO3)2·6H2O溶于10～20mL甲醇或乙醇中，并将硝酸锌溶液滴加到上述配体溶液中，继续回流2～6小时，析出固体产物，过滤，产物依次用甲醇或乙醇、乙醚洗涤，真空干燥得黄色固体粉末，将该固体粉末溶于二甲基亚砜成为饱和溶液，室温静置挥发，约4～6周后析出黄色块状晶体。
本发明制得的三唑席夫碱锌配合物具有抑制PTP1B活性以及体外抑制乳腺癌(MCF-7)细胞增殖的能力，该类配合物可作为PTP1B抑制剂，并且在制备抗肿瘤药物中应用。
本发明的优点和效果：本发明的配合物合成方法简单，配合物稳定，晶体易得，不仅能够有效抑制PTP1B活性，而且对体外乳腺癌(MCF7)细胞增殖有明显的抑制作用，为以PTP1B为作用靶点的抗肿瘤治疗提供了一种新的药物开发途径。
附图说明
图1本发明三唑席夫碱锌配合物的晶体结构图(对称代码A 1–x,0.5+y,1.5-z)
图2本发明三唑席夫碱锌配合物的晶体结构沿b轴方向延伸结构图
图3本发明三唑席夫碱锌配合物抑制PTP1B活性的IC50测定图
图4本发明三唑席夫碱锌配合物与PTP1B相互作用的荧光图
图5不同浓度梯度的本发明三唑席夫碱锌配合物对MCF-7细胞增殖的影响
具体实施方式
下面结合附图和实例对本发明作进一步说明。
实施例1
配合物的制备
(1)前提配体3-甲基-4-氨基-5-巯基-1,2,4-三唑按文献方法制备。
(2)参照文献方法合成5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱配体。
5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱化合物的元素分析测定：C10H9ClN4OS，括号内为理论值(％)：C,44.78(44.70)；H,3.35(3.38)；N,21.02(20.85)。
(3)合成本发明5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱锌配合物：将1mmol(0.269g)5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱配体溶于30mL甲醇或乙醇，滴加1mmol(150μl)的三乙胺，加热搅拌使配体溶解，然后将1mmol(0.297g)六水合硝酸锌溶于15mL甲醇或乙醇溶液中，将硝酸锌溶滴加到上述配体溶液中，继续回流2～6小时，析出固体产物，过滤，产物依次用甲醇或乙醇、乙醚洗涤，真空干燥得黄色固体粉末，将该固体粉末溶于二甲基亚砜成为饱和溶液，室温静置挥发，约4周后析出黄色块状晶体。
配合物单晶结构
在高倍显微镜下，挑选规则、透明的块状单晶颗粒,在北京同步辐射光源，1W2B线站，2.2GeV的工作电压，使用MARCCD-165探测器，入射收集其晶体的衍射数据。收集过程温度为100K氮气氛围，经HKL2000还原数据.，并用SHELXTL-NT 5.10版程序包解析出配合物晶体结构。配合物的晶体结构如附图1和图2，有关晶体其它一些详细的信息列于表1和表2。在该席夫碱锌配合物中，中心金属锌与一个席夫碱配体中三唑硫酮的硫原子、酰胺氮原子和酚基氧原子配位，同时还与另外一个分子配体的三唑氮配位，以及溶剂分子二甲基亚砜的氧配位形成一个四方锥的配位构型，同时各个结构单元相互连接，形成一个空间网状结构。
表1席夫碱锌配合物的晶胞及测量参数
表2席夫碱锌配合物的部分主要键长和键角数据(°)。
实施例2本发明席夫碱锌配合物对PTP活性抑制的IC50值测定
以pNPP为底物测定了配合物对PTP1B活性的抑制作用，反应体系在pH＝7.2的MOPS缓冲溶液进行，37℃下恒温反应30min，然后用2μL 0.1M的pNPP启动反应，放置约半个小时以后加5μL 2M的NaOH终止反应，用酶标仪测定A405的紫外吸收值，通过测定A405的紫外吸收确定生成的pNP的量，以抑制百分数为纵坐标，配合物浓度对数值为横坐标，作图得到抑制曲线并得出它们相应的IC50值，如图3所示，锌配合物能够有效地抑制PTP1B活性，IC50值为4.6×10-7M。
实施例3本发明席夫碱锌配合物对PTP的荧光淬灭作用
蛋白质分子中由于含有酪氨酸和色氨酸残而使其具有天然荧光，当向蛋白溶液中加入一些小分子后，小分子与蛋白分子的结合会影响到蛋白分子微环境的变化，从而引起蛋白分子的荧光变化，可以借助蛋白分子的荧光信号的变化来研究他们的作用模式和机理。所以我们研究了本发明配合物对PTP1B的荧光淬灭作用。图4所示为扣除了配合物本身的荧光强度之后，配合物滴定PTP1B的荧光光谱图，从图中可以看出随着配合物的浓度逐渐增加，PTP1B在341nm处的荧光强度逐渐减弱，直至降到一定程度后，荧光强度几乎不变，同时在484nm处出现一个新的荧光峰，且其荧光强度随着配合物浓度的增加而增加，这可能是配合物与PTP1B结合形成的复合物的荧光峰，这个实验结果进一步证明了锌配合物与PTP1B之间的相互作用。
实施例4本发明席夫碱锌配合物体外抗肿瘤活性测定
用MTT法检测了锌配合物对肿瘤细胞MCF-7细胞增殖的影响，取对数生长期的肿瘤细胞经过消化、离心、收集后配成1mL的细胞悬液。吸取适量体积的上述细胞悬液将其稀释成20mL细胞密度约为1.25×104个/mL的细胞悬液，将其均匀接种于96孔培养板，每孔滴加200μL。将96孔板放在CO2培养箱中孵育12h后，加入已配好的一系列浓度的配合物，另设对照组加入等体积的混合溶剂(DMSO(10％)+0.85％NaCl(90％))，每组分别设6个复孔。继续放入CO2培养箱中24h后，每孔加入5mg/mL的MTT溶液20μL，再次孵育4h后，取出96孔板，小心吸去孔中上清液，吸净后每孔加入150μL的DMSO溶液，等待10min，待底部结晶状固体完全溶解后用酶标仪测得各孔溶液490nm处的吸光度值A。以药物浓度为横坐标，细胞存活率为纵坐标绘制细胞生长曲线。
细胞存活率(％)＝(A实验组/A对照组)×100
图5表示配合物在24小时内对MCF-7增殖的影响，从图中可以看出，MCF-7细胞的存活率基本上是随着配合物浓度的增加而降低，仅仅作用24小时之后，当配合物浓度为10-4M时，肿瘤细胞MCF-7的存活率就小于60％，当配合物浓度为0.5mM时，肿瘤细胞MCF-7的存活率小于30％，有明显的抑制作用。由此可见，该配合物有一定的抗肿瘤活性。
Claims (5)
1.一种三唑席夫碱锌配合物，其特征在于结构式为：
2.如权利要求1所述的一种三唑席夫碱锌配合物的制备方法，其特征在于，包括如下步骤：
(1)合成3-甲基-4-氨基-5-巯基-1,2,4-三唑；
(2)合成5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱配体；
(3)合成席夫碱锌配合物：按每毫摩尔配体加入20～40mL甲醇，将5-氯水杨醛缩-3-甲基-4-氨基-5-巯基-1,2,4-三唑席夫碱配体溶于甲醇中，滴加等摩尔量的三乙胺，加热搅拌使配体完全溶解，然后将等摩尔量Zn(NO3)2·6H2O溶于10～20mL甲醇中，并将硝酸锌溶液滴加到上述配体溶液中，继续回流2～6小时，析出固体产物，过滤，产物依次用甲醇、乙醚洗涤，真空干燥得黄色固体粉末，将该固体粉末溶于二甲基亚砜成为饱和溶液，室温静置挥发，4～6周后析出黄色块状晶体。
3.如权利要求2所述的一种三唑席夫碱锌配合物的制备方法，其特征在于，步骤(3)中所述的甲醇用乙醇替代。
4.如权利要求1所述的一种三唑席夫碱锌配合物在制备抑制PTP1B活性制剂中的应用。
5.如权利要求1所述的一种三唑席夫碱锌配合物在制备抗肿瘤药物中的应用。
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| Title |
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| 新含硫席夫碱—3-烷基-4-氨基-5-巯基-1,2,4-三唑衍生物的合成研究;柳翠英等;《化学试剂》;20011231;第23卷(第6期);第344-345页 * |
| 新型1,2,4-三唑类衍生物的合成及表征;武现丽等;《化学试剂》;20091231;第31卷(第10期);第785-788页 * |
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