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N-羟乙基-N-苯并咪唑基甲基乙二胺二乙酸与第12族金属及钒的配合物——钒配合物的合成、结构及生物活性

Complexes of N-hydroxyethyl-N-benzimidazolylmethylethylenediaminediacetic acid with group 12 metals and vanadium-Synthesis, structure and bioactivity of the vanadium complex.

作者信息

Habala Ladislav, Bartel Caroline, Giester Gerald, Jakupec Michael A, Keppler Bernhard K, Rompel Annette

机构信息

Institut für Biophysikalische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria; Department of Chemical Theory of Drugs, Faculty of Pharmacy, Comenius University, Kalinciakova 8, SK-832 32 Bratislava, Slovakia.

Institut für Anorganische Chemie, Fakultät für Chemie, Universität Wien, Althanstr. 14, A-1090 Wien, Austria.

出版信息

J Inorg Biochem. 2015 Jun;147:147-52. doi: 10.1016/j.jinorgbio.2015.04.004. Epub 2015 Apr 11.

Abstract

Four new complexes of group 12 metals [Zn(II), Cd(II) and Hg(II)], along with vanadyl bound to the ligand N-hydroxyethyl-N-benzimidazolylmethylethylenediaminediacetic acid, have been synthesized and characterized. The structure of the complexes with Zn(II), Hg(II) and V(IV) was determined by X-ray structural analysis. In all observed cases, the symmetry of these complexes was found to be distorted octahedral. The inhibition of protein tyrosine phosphatase 1B by the vanadium(IV) complex was demonstrated. The cytotoxicity of the vanadium(IV) complex was tested in vitro against three cancer cell lines, with a comparison of the activity of the free ligand and of vanadyl acetylacetonate and sodium orthovanadate. The IC50 values of the complex were in the range of 9 to 21μM. Remarkably, cytotoxic potency in the multidrug-resistant non-small cell lung cancer cell line A549 was at least as high as in the broadly chemosensitive ovarian teratocarcinoma cell line CH1(PA-1).

摘要

已合成并表征了四种新的第12族金属(锌(II)、镉(II)和汞(II))配合物,以及与配体N-羟乙基-N-苯并咪唑基甲基乙二胺二乙酸结合的氧钒配合物。通过X射线结构分析确定了锌(II)、汞(II)和钒(IV)配合物的结构。在所有观察到的情况下,这些配合物的对称性均为畸变八面体。证明了钒(IV)配合物对蛋白酪氨酸磷酸酶1B的抑制作用。在体外测试了钒(IV)配合物对三种癌细胞系的细胞毒性,并比较了游离配体、乙酰丙酮氧钒和原钒酸钠的活性。该配合物的IC50值在9至21μM范围内。值得注意的是,该配合物在多药耐药非小细胞肺癌细胞系A549中的细胞毒性效力至少与广泛化疗敏感的卵巢畸胎瘤细胞系CH1(PA-1)一样高。

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