双席夫碱氧钒(Ⅳ)配合物抑制多种PTPs活性研究  

Inhibition of the Activity of Several PTPs by Oxovanadium Complexes with Schiff Base Ligands

作　　者：王矗 宋澳旋 李鹏利 袁彩霞[1] WANG Chu;SONG Aoxuan;LI Pengli;YUAN Caixia(Institute of Molecular Science,the Key Laboratory of Chemical Biology and Molecular Engineering of the Ministry of Education,Taiyuan 030006,China;School of Chemistry and Chemical Engineering,Shanxi University,Taiyuan 030006,China)

机构地区：[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,山西太原030006 [2]山西大学化学化工学院,山西太原030006

出　　处：《山西大学学报（自然科学版）》2021年第6期1156-1163,共8页Journal of Shanxi University(Natural Science Edition)

基　　金：国家自然科学基金(21471092);山西省自然科学基金(201901D111014)。

摘　　要：文章合成表征了3个水杨醛缩邻苯二胺衍生物双席夫碱氧钒配合物(V^(Ⅳ)OL1、V^(Ⅳ)OL2和V^(Ⅳ)OL3),研究了它们对4种蛋白酪氨酸磷酸酶(PTPs,包括PTP1B、TCPTP、SHP-1和PTP-Meg2)活性的抑制作用。结果表明这些氧钒配合物抑制PTPs活性的IC_(50)值范围是0.015μmol/L~0.116μmol/L,其中V^(Ⅳ)OL1表现出很强的TCPTP和PTP-Meg2抑制作用(IC_(50)值分别为0.015μmol/L和0.016μmol/L),而V^(Ⅳ)OL2抑制TCPTP活性的IC_(50)值为0.116μmol/L,显示出相对较弱的TCPTP抑制能力。此外,V^(Ⅳ)OL3抑制PTP1B活性的IC_(50)值为0.015μmol/L,比经典的潜在抗糖尿病化合物联麦氧钒(BMOV)抑制PTP1B活性的能力高出几十倍,几乎是目前抑制活性最强的二氧钒配合物。虽然这些配合物对各种酶的抑制能力有一定差异,但是与硫酸氧钒的抑制作用相比,该类配合物对4种PTPs都表现出有效的抑制作用,是一类多靶点PTPs抑制剂。Three oxovanadium complexes of Schiff base condensated from salicylaldehyde and 4-substitured-o-phenylenediamine were synthesized and characterized,and the IC_(50) values of their inhibition against four protein tyrosine phosphatases(PTP1B,TCPTP,SHP-1,and PTP-Meg)were also determined.The IC_(50) values of these complexes ranged from 0.015μmol/L to 0.116μmol/L.Of them,V^(Ⅳ)OL1 shows the strong potent inhibition against TCPTP and PTP-Meg2 with IC_(50) values of 0.015μmol/L and 0.016μmol/L,respectively,while V^(Ⅳ)OL2 demonstrated the relatively weak inhibition against TCPTP,with the highest IC_(50) value(0.116μmol/L).In addition,the IC_(50)of V^(Ⅳ)OL3 against PTP1 B is 0.015μmol/L.The inhibition ability are about tens times higher than that of Bis(maltolato)oxovanadium(BMOV)with potential anti-diabetic effect,which is almost the most potent PTP1B inhibitor based VO2+complexes recently reported.Moreover,these complexes exhibited different inhibitory ability against four PTPs,they are PTPs inhibitors with multiple targets because of the efficient inhibition against four PTPs compared with those of VOSO_(4).

关 键 词：氧钒配合物 蛋白酪氨酸磷酸酶 抑制剂 席夫碱 

分 类 号：O61[理学—无机化学]