Institute of Molecular Science, Key Laboratory of Chemical Biology and Molecular Engineering of the Education Ministry, Shanxi University, Taiyuan, People's Republic of China.
Biometals. 2011 Dec;24(6):993-1004. doi: 10.1007/s10534-011-9460-3. Epub 2011 May 27.
A series of copper complexes with multi-benzimidazole derivatives, including mono- and di-nuclear, were synthesized and characterized by Fourier transform IR spectroscopy, UV-Vis spectroscopy, elemental analysis, electrospray ionization mass spectrometry. The speciation of Cu/NTB in aqueous solution was investigated by potentiometric pH titrations. Their inhibitory effects against human protein tyrosine phosphatase 1B (PTP1B), T-cell protein tyrosine phosphatase (TCPTP), megakaryocyte protein tyrosine phosphatase 2 (PTP-MEG2), srchomology phosphatase 1 (SHP-1) and srchomology phosphatase 2 (SHP-2) were evaluated in vitro. The five copper complexes exhibit potent inhibition against PTP1B, TCPTP and PTP-MEG2 with almost same inhibitory effects with IC(50) at submicro molar level and about tenfold weaker inhibition versus SHP-1, but almost no inhibition against SHP-2. Kinetic analysis indicates that they are reversible competitive inhibitors of PTP1B. Fluorescence study on the interaction between PTP1B and complex 2 or 4 suggests that the complexes bind to PTP1B with the formation of a 1:1 complex. The binding constant are about 1.14 × 10(6) and 1.87 × 10(6) M(-1) at 310 K for 2 and 4, respectively.
一系列带有多苯并咪唑衍生物的铜配合物，包括单核和双核配合物，通过傅里叶变换红外光谱、紫外可见光谱、元素分析和电喷雾质谱进行了合成和表征。通过电位 pH 滴定法研究了 Cu/NTB 在水溶液中的形态。评估了它们对人蛋白酪氨酸磷酸酶 1B（PTP1B）、T 细胞蛋白酪氨酸磷酸酶（TCPTP）、巨核细胞蛋白酪氨酸磷酸酶 2（PTP-MEG2）、srchomology 磷酸酶 1（SHP-1）和 srchomology 磷酸酶 2（SHP-2）的体外抑制作用。这五个铜配合物对 PTP1B、TCPTP 和 PTP-MEG2 具有很强的抑制作用，其抑制效果几乎相同，IC50 值在亚微摩尔水平，对 SHP-1 的抑制作用约弱 10 倍，但对 SHP-2 几乎没有抑制作用。动力学分析表明它们是 PTP1B 的可逆竞争性抑制剂。PTP1B 与配合物 2 或 4 之间相互作用的荧光研究表明，这些配合物与 PTP1B 结合形成 1:1 复合物。结合常数分别约为 1.14×106 和 1.87×106 M-1，在 310 K 时分别对应于 2 和 4。
