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双核钒配合物增强胰岛素活性的研究:5-氯水杨醛乙二胺氧钒(V)及其通透性和细胞毒性。

Insulin-enhancing activity of a dinuclear vanadium complex: 5-chloro-salicylaldhyde ethylenediamine oxovanadium(V) and its permeability and cytotoxicity.

机构信息

Deparment of Chemistry, Yunnan University, Kunming 650091, China.

出版信息

J Inorg Biochem. 2010 Aug;104(8):851-7. doi: 10.1016/j.jinorgbio.2010.03.018. Epub 2010 Apr 8.

DOI:10.1016/j.jinorgbio.2010.03.018
PMID:20434776
Abstract

A new insulin-enhancing oxovanadium complex 5-chloro-salicylaldhyde ethylenediamine oxovanadium (V) ([V(2)O(2)(mu-O)(2)L(2)]) has been synthesized. The complex was characterized by a variety of physical methods, including X-ray crystallography. The X-ray diffraction analysis show a dinuclear complex of two six-coordinate vanadium centers doubly bridged by the oxygen atoms of the Schiff base ligand with a V(2)O(2) diamond core. The complex was administered intragastrically to STZ-diabetic rats for 2 weeks. The biological activity results show that the complex at the dose of 10.0 and 20.0 mg V kg(-1), could significantly decrease the blood glucose level and ameliorate impaired glucose tolerance in STZ-diabetic rats. That results suggested that the complex exerts an antidiabetic effect in STZ-diabetic rats. Furthermore, the complex ([V(2)O(2)(mu-O)(2)L(2)]) had permeability above 10(-5)cm/s. The experimental results suggested that the vanadium complex permeates via a passive diffusion mechanism. It was also suggested the complex with salen-type ligands has good lipophilic properties and better oral administration. The cytotoxicity of the complex ([V(2)O(2)(mu-O)(2)L(2)]) on Caco-2 cells was measured by a decrease of cell viability using the MTT assay suggesting that the chlorine atom at C4 of complex [V(2)O(2)(mu-O)(2)L(2)] increased cytotoxicity for vanadium complexes.

摘要

一种新的胰岛素增强型氧钒配合物 5-氯水杨醛乙二胺氧钒(V) ([V(2)O(2)(μ-O)(2)L(2)]) 已被合成。该配合物通过多种物理方法进行了表征,包括 X 射线晶体学。X 射线衍射分析表明,该配合物为双核配合物,两个六配位的钒中心通过希夫碱配体的氧原子双桥接,具有 V(2)O(2) 金刚石核。该配合物被灌胃给予 STZ 糖尿病大鼠 2 周。生物活性结果表明,该配合物在 10.0 和 20.0 mg V kg(-1)剂量下,可显著降低血糖水平并改善 STZ 糖尿病大鼠的葡萄糖耐量受损。结果表明,该配合物在 STZ 糖尿病大鼠中发挥抗糖尿病作用。此外,该配合物([V(2)O(2)(μ-O)(2)L(2)])的通透性超过 10(-5)cm/s。实验结果表明,该钒配合物通过被动扩散机制渗透。还表明,具有沙利度胺型配体的配合物具有良好的亲脂性和更好的口服给药。通过 MTT 测定法测量配合物([V(2)O(2)(μ-O)(2)L(2)])对 Caco-2 细胞的细胞毒性,表明配合物[V(2)O(2)(μ-O)(2)L(2)]中氯原子在 C4 增加了钒配合物的细胞毒性。

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