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新型设计的钯(II)配合物的光谱和细胞毒性研究:以β-乳球蛋白和K562为靶点。

Spectroscopic and cytotoxic studies of the novel designed palladium(II) complexes: beta-lactoglobulin and K562 as the targets.

作者信息

Divsalar A, Saboury A A, Yousefi R, Moosavi-Movahedi A A, Mansoori-Torshizi H

机构信息

Institute of Biochemistry and Biophysics, University of Tehran, Tehran, Iran.

出版信息

Int J Biol Macromol. 2007 Mar 10;40(4):381-6. doi: 10.1016/j.ijbiomac.2006.09.015. Epub 2006 Oct 4.

Abstract

Since palladium complexes have been reported to show fewer side effects relative to other heavy metal anticancer compounds, in this study a new class of four structurally related anticancer Pd(II) complexes including 2,2'-bipyridin-n-butyl dithiocarbamato Pd(II) nitrate (Com-1), 2,2'-bipyridin-n-hexyl dithiocarbamato Pd(II) nitrate (Com-2), 2,2'-bipyridin glycinato Pd(II) nitrate (Com-3) and 2,2'-bipyridin octylglycinato Pd(II) nitrate (Com-4) was designed. The effect of four synthesized ligands on the protein structure and cell proliferation were investigated. Whey carrier proteins beta-lactoglobulin-A and-B (BLG-A and-B) and chronic myelogenous leukemia cell line K562 were the targets. Fluorescence and CD instruments were used to assess effect of the ligands on the protein structure. Growth inhibitory effect of the Pd(II) complexes towards the cancer cells was measured using 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide (MTT) assay. Results of fluorescence studies revealed that the complexes had no dithiocarbamate moiety (compounds 3 and 4) could quench the intrinsic fluorescence emission of the proteins at lower concentrations than those had such moiety (compounds 1 and 2). The far-UV-CD studies revealed that the regular secondary structure of BLG-A and -B did not show any noticeable alteration upon interaction with different of Pd(II)-complexes. The results of cell proliferation assay also displayed that Com-1 and Com-2 had more growth inhibitory activity against K562, than Com-3 and Com-4. Our results suggested that addition of dithiocarbamate moiety to structure of Pd(II) complexes probably has important role to improve the antiproliferative properties of the anticancer ligands and fewer effects on the carrier protein structure.

摘要

由于据报道钯配合物相对于其他重金属抗癌化合物显示出较少的副作用,因此在本研究中设计了一类新的四种结构相关的抗癌钯(II)配合物,包括2,2'-联吡啶 - n - 丁基二硫代氨基甲酸钯(II)硝酸盐(化合物1)、2,2'-联吡啶 - n - 己基二硫代氨基甲酸钯(II)硝酸盐(化合物2)、2,2'-联吡啶甘氨酸钯(II)硝酸盐(化合物3)和2,2'-联吡啶辛基甘氨酸钯(II)硝酸盐(化合物4)。研究了四种合成配体对蛋白质结构和细胞增殖的影响。乳清载体蛋白β-乳球蛋白-A和-B(BLG-A和-B)以及慢性粒细胞白血病细胞系K562为研究对象。使用荧光和圆二色性仪器评估配体对蛋白质结构的影响。使用3-(4,5-二甲基噻唑-2-基)-2,5-二苯基溴化四氮唑(MTT)法测量钯(II)配合物对癌细胞的生长抑制作用。荧光研究结果表明,不含二硫代氨基甲酸盐部分的配合物(化合物3和4)在比含有该部分的配合物(化合物1和2)更低的浓度下就能淬灭蛋白质的固有荧光发射。远紫外圆二色性研究表明,BLG-A和-B的规则二级结构在与不同的钯(II)配合物相互作用时未显示出任何明显变化。细胞增殖试验结果还显示,化合物1和化合物2对K562的生长抑制活性比化合物3和化合物4更强。我们的结果表明,在钯(II)配合物结构中添加二硫代氨基甲酸盐部分可能对改善抗癌配体的抗增殖特性具有重要作用,并且对载体蛋白结构的影响较小。

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