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新型 Cd(II)和 Zn(II)配合物的合成、结构和表征:2-糠醛缩硒代氨基脲与 2-糠醛缩氨基硫脲的缩合产物。合成配合物及相关硒代缩氨基硫脲配合物的体外抗肿瘤活性。

Synthesis, structure and characterization of novel Cd(II) and Zn(II) complexes with the condensation product of 2-formylpyridine and selenosemicarbazide Antiproliferative activity of the synthesized complexes and related selenosemicarbazone complexes.

机构信息

Institute for Oncology and Radiology of Serbia, Department of Experimental Oncology, Laboratory for Experimental Pharmacology, Pasterova 14, Belgrade, Serbia.

出版信息

J Inorg Biochem. 2010 Jun;104(6):673-82. doi: 10.1016/j.jinorgbio.2010.02.009. Epub 2010 Mar 10.

Abstract

Two novel Cd(II) and Zn(II) complexes with the condensation product of 2-formylpyridine and selenosemicarbazide were synthesized. The structure of Cd(II) complex was determined by X-ray crystallography. The ligand is coordinated in a neutral form via pyridine and azomethine nitrogen atoms and the selenium donor. The cadmium ion completes its five-coordination by two chloride ligands, forming a square-pyramidal geometry. The structure of Zn(II) complex was established by analysis of spectroscopic data, which indicated coordination of the ligand as a bidentate via the selenium and the azomethine nitrogen atoms. The cytotoxic activity of the newly synthesized complexes, as well as if five structurally related complexes and the ligand evaluated against eight tumor cell lines. The new Cd(II) complex showed the highest activity similar to cisplatin with IC50 less than 10muM for all cell lines. Cell cycle distribution and apoptosis study showed that Cd(II) complex and cisplatin might have some similarity in anticancer activity, which was not the case for cisplatin and other studied complexes. Effects of the complexes on matrix metalloproteinases (MMPs) MMP-9 and MMP-2 was also studied. Cd(II) and Zn(II) complexes and cisplatin increased MMP-2 activity in supernatants of tested cells, while Ni(II) complex with the same ligand decreased the activity, implying a possible activity in preventing tumor invasion and metastasis processes.

摘要

合成了两个新的 Cd(II) 和 Zn(II) 配合物,其配体是 2- 甲酰基吡啶和硒代缩氨基脲的缩合产物。Cd(II) 配合物的结构通过 X 射线晶体学确定。配体以中性形式通过吡啶和亚氨基氮原子以及硒供体配位。镉离子通过两个氯离子完成其五配位,形成四方锥几何形状。Zn(II) 配合物的结构通过光谱数据分析确定,表明配体通过硒和亚氨基氮原子作为双齿配位。评估了新合成的配合物以及与五种结构相关的配合物和配体对八种肿瘤细胞系的细胞毒性活性。新合成的 Cd(II) 配合物表现出与顺铂相似的最高活性,对所有细胞系的 IC50 均小于 10μM。细胞周期分布和凋亡研究表明,Cd(II) 配合物和顺铂在抗癌活性方面可能具有一些相似性,而不是顺铂和其他研究的配合物。还研究了配合物对基质金属蛋白酶 (MMPs) MMP-9 和 MMP-2 的影响。Cd(II) 和 Zn(II) 配合物以及顺铂增加了测试细胞上清液中 MMP-2 的活性,而具有相同配体的 Ni(II) 配合物降低了活性,这表明它们可能具有预防肿瘤侵袭和转移过程的活性。

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