水杨醛缩芳胺席夫碱铜(Ⅱ)配合物抑制蛋白酪氨酸磷酸酶活性研究

引用本文: 袁彩霞, 兰淑芬, 卢丽萍. 水杨醛缩芳胺席夫碱铜(Ⅱ)配合物抑制蛋白酪氨酸磷酸酶活性研究[J]. 无机化学学报, 2015, (5): 915-922. doi: 10.11862/CJIC.2015.127 shu

Citation: YUAN Cai-Xia, LAN Shu-Fen, LU Li-Ping. Evaluation of Cu(Ⅱ) Complexes with Schiff Base of Salicylanilide as the Inhibitors of Protein Tyrosine Phosphatases[J]. Chinese Journal of Inorganic Chemistry, 2015, (5): 915-922. doi: 10.11862/CJIC.2015.127 shu

水杨醛缩芳胺席夫碱铜(Ⅱ)配合物抑制蛋白酪氨酸磷酸酶活性研究

1.
山西大学分子科学研究所, 化学生物学与分子工程教育部重点实验室, 太原 030006

通讯作者: 卢丽萍 luliping@sxu.edu.cn

基金项目:
国家自然科学基金(No.21001070,21171109,21471092) (No.21001070,21171109,21471092)

高等学校博士学科点专项科研基金(No.20121401110005) (No.20121401110005)

山西省自然科学基金(No.2011021006-2) (No.2011021006-2)

山西省回国留学人员科研项目(No.2012-004)资助项目。 (No.2012-004)

摘要: 为了探讨席夫碱配体上取代基变化对其配合物抑制蛋白酪氨酸磷酸酶(PTPs)活性的影响,合成表征了水杨醛缩芳胺席夫碱铜(Ⅱ)配合物[Cu(X-pimp)₂](X=Cl,Br和Acetyl),用紫外光谱滴定和pH电位滴定研究了[Cu(Cl-pimp)₂]的溶液结构,并测定了3个配合物抑制4种PTPs活性的IC₅₀值。结果表明它们都能够有效抑制PTP1B和TCPTP(0.20μmol·L^-1< IC₅₀< 0.31μmol·L^-1),但对SHP-1的抑制较弱且对SHP-2几乎无抑制作用。分析并与文献结果比较发现,席夫碱配体上苯胺对位取代基类型的改变不会显著影响其抑制作用,但取代基位置的改变可能会影响其选择性。稳态动力学研究表明[Cu(Cl-pimp)₂]能够非竞争性抑制PTP1B活性,而荧光光谱实验表明二者形成了键合常数为9.3×10⁶L·mol^-1的1:1复合物。我们推测,配合物可能结合在PTP1B非活性区域,间接导致活性中心结构变化,从而抑制其活性。

关键词:

席夫碱;铜(Ⅱ)配合物;蛋白酪氨酸磷酸酶;抑制剂;取代基效应

English

Evaluation of Cu(Ⅱ) Complexes with Schiff Base of Salicylanilide as the Inhibitors of Protein Tyrosine Phosphatases

1.
Institute of Molecular Science, the Key Laboratory of Chemical Biology and Molecular Engineering of Education Ministry, Shanxi University, Taiyuan 030006, China

Corresponding author: 卢丽萍 luliping@sxu.edu.cn

Received Date: 17 November 2014
Fund Project:
国家自然科学基金(No.21001070,21171109,21471092)

高等学校博士学科点专项科研基金(No.20121401110005)

山西省自然科学基金(No.2011021006-2)

山西省回国留学人员科研项目(No.2012-004)资助项目。

Abstract: To improve the inhibitory selectivity and explore the substitution effect of the Schiff base ligands on the inhibitory effect of the complex against the PTPs, three Cu(Ⅱ) complexes, [Cu(X-pimp)₂] (X-pimp=2-((4-X-phenylimino)methyl) phenol), X=Cl, Br, and Acetyl), were prepared and characterized by X-ray, EA, IR, UV-Vis and ESI-MS. Taking [Cu(Cl-pimp)₂] complex as an example, the solution species distribution with different pH values and the main existing form under the pH neutral condition were investigated using both the pHpotentiometric and UV titrations, indicating that the ration of Cl-pimp ligand and Cu(Ⅱ) ion in the complex was 2:1 in an aqueous solution and [Cu(Cl-pimp)₂H_-1]^- is the main existing form in the pHneutral condition. Then the inhibitory activities of these complexes against above-mentioned protein tyrosine phosphatase 1B(PTP1B), T-cell protein tyrosine phosphatase(TCPTP), Src homology phosphatase 1 (SHP-1), and Src homology phosphates 2 (SHP-2) was evaluated using IC₅₀ values. The results revealed that these three complexes showed similar inhibitory behaviours, i.e. potent effect against PTP1B and TCPTP (0.20 μmol·L^-1 50 <0.31 μmol·L^-1), the relatively lower effect against SHP-1 (2.7 μmol·L^-1 < IC₅₀ <4.7 μmol·L^-1), while negligible effect against SHP-2 (IC₅₀ >100 μmol·L^-1), which indicated that the type of substituents on the papa position of phenylimino of the Schiff base ligand did not influence the inhibitory effect of the complexes against PTPs obviously. However, comparing the current results to that of the above-mentioned previous work, we can find that the change in the position of the substituents may change the selectivity of inhibitory effect of the complexes against PTPs. The interactions between the complexes and PTPs were studied using [Cu(Cl-pimp)₂] and PTP1B as the representatives. The kinetics assays showed that the complex inhibited PTP1B in a non-competitive mode and the inhibition constant was calculated to be 0.35 μmol·L^-1. The fluorescence titration revealed that the complex bound to PTp1B with the molar ration of 1:1 and the binding constant of 9.3×10⁶ L·mol^-1. We infer that the [Cu(Cl-pimp)₂] complex may bind firmly to inactive area of PTP1B and indirectly lead to the structural changes to the active center, which inhibits the activity of PTP1B.

Key words:

Schiff base;Cu(Ⅱ) complex;protein tyrosine phosphatases;inhibitor;substituent effect

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1.
沈阳化工大学材料科学与工程学院沈阳 110142

水杨醛缩芳胺席夫碱铜(Ⅱ)配合物抑制蛋白酪氨酸磷酸酶活性研究

通讯作者: 卢丽萍 luliping@sxu.edu.cn

English

Evaluation of Cu(Ⅱ) Complexes with Schiff Base of Salicylanilide as the Inhibitors of Protein Tyrosine Phosphatases

Corresponding author: 卢丽萍 luliping@sxu.edu.cn

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

水杨醛缩芳胺席夫碱铜(Ⅱ)配合物抑制蛋白酪氨酸磷酸酶活性研究

通讯作者: 卢丽萍 luliping@sxu.edu.cn

English

Evaluation of Cu(Ⅱ) Complexes with Schiff Base of Salicylanilide as the Inhibitors of Protein Tyrosine Phosphatases

Corresponding author: 卢丽萍 luliping@sxu.edu.cn

CCS Chemistry：嵌段共聚物自组装成 “三明治”二维有机材料，实现纳米级压力传感功能

CCS Chemistry：颜徐州、鲍哲南： 你的皮肤可能是一片SPMs

CCS Chemistry：工作高效不疲劳，只须让催化剂动起来

CCS Chemistry：静电组装导向聚合- 聚电解质纳米凝胶量化制备新策略

CCS Chemistry：金黄色葡萄球菌醛基脱氢酶是如何识别特异性底物的？

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通讯作者: 陈斌, bchen63@163.com

中国化学会秘书处

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