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化学学报
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化学学报 ›› 2009, Vol. 67 ›› Issue (9): 929-936. 上一篇    下一篇

研究论文

含氮杂环氧钒配合物对PTP1B和ALP的抑制活性研究

高晓丽a 卢丽萍*,a 朱苗力*,a 袁彩霞a 马俊锋b 付学奇*,b

  

  1. (a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)
    (b吉林大学生命科学学院 Edmond H. Fischer细胞信号传导实验室 长春 130023)

  • 投稿日期:2009-01-05 修回日期:2009-03-26 发布日期:2009-05-14
  • 通讯作者: 朱苗力

Inhibitory Activities of Some Oxovanadium Complexes with N-Heterocyclic Ligands against PTP1B/ALP

Gao, Xiaoli a Lu, Liping *,a Zhu, Miaoli *,a Yuan, Caixia a
Ma, Junfeng b Fu, Xueqi *,b

  

  1. (a Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering, Ministry of Education, Shanxi University, Taiyuan 030006)
    (b Edmond H. Fischer Signal Transduction Laboratory, College of Life Sciences, Jilin University, Changchun 130023)
  • Received:2009-01-05 Revised:2009-03-26 Published:2009-05-14
  • Contact: Zhu, Miaoli

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1439

被引次数

35 | 6

蛋白酪氨酸磷酸酶1B (protein tyrosine phosphatase 1B, PTP1B)是当前开发治疗糖尿病药物的优秀靶标, 也是钒配合物抗糖尿病作用相关的重要靶蛋白. 研究了三种含氮平面杂环螯合配体2,2’-联咪唑(L1), 2,2’-联吡啶(L2), 1,10-邻菲咯啉(L3)的氧钒配合物对PTP1B以及碱性磷酸酶(alkaline phosphatase, ALP)的体外抑制作用. 结果表明, 1∶1和2∶1型配位的氧钒化合物均表现出对PTP1B较强的抑制活性, IC50值在120～260 nmol/L间, 抑制能力接近双麦芽酚氧钒配合物(BMOV). 抑制动力学实验表明这些氧钒配合物对PTP1B的抑制模式均为竞争性抑制, 抑制常数在20～160 nmol/L. 其对PTP1B抑制活性较ALP高103倍, 表明氧钒配合物对两种磷酸酶的抑制具有一定的选择性.

关键词: 氧钒配合物, 蛋白酪氨酸磷酸酶1B, 碱性磷酸酶, 抑制剂

Protein tyrosine phosphatase 1B (PTP1B) has been emerging as an attractive drug target for diabetes disease treatment, and is also associated with the anti-diabetes effects of vanadium complexes. The inhibitory activities against PTP1B and alkaline phosphatase (ALP) by oxovanadium complexes with 2,2’-biimidazole (L1), 2,2’-bipyridine (L2) and 1,10-phenanthroline (L3) have been investigated in vitro. The complexes of [VO(L1～L3)] and [VO(L1～L3)2] have been found to be potent inhibitors against PTP1B (IC50＝120～260 nmol/L). Their inhibitory ability is close to bis(maltolato)oxovanadium (BMOV). Kinetics assays suggest that these complexes inhibit PTP1B in a classical competitive manner (Ki＝20～160 nmol/L). The inhibitory activities of these complexes against PTP1B are 103 fold higher than that against ALP, showing a selectivity against both phosphatases.

Key words: oxovanadium complex, protein tyrosine phosphatase 1B, alkaline phosphatase, inhibitor