Department of Chemistry, Wayne State University, 5101 Cass Ave., Detroit, MI 48202, USA.
Barbara Ann Karmanos Cancer Institute, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Department of Oncology, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Department of Pathology, School of Medicine, Wayne State University, Detroit, MI 48201, USA; Department of Pharmacology, School of Medicine, Wayne State University, Detroit, MI 48201, USA.
J Inorg Biochem. 2014 Mar;132:96-103. doi: 10.1016/j.jinorgbio.2013.12.012. Epub 2014 Jan 8.
In this paper we report on the synthesis of five metal complexes coordinated to the [NN'O] ligand HL(iodo) (2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol), namely [Al(III)(L(iodo))2]ClO4 (1), [Cd(II)(L(iodo))Cl]·H2O (2), [Hg(II)(L(iodo))2]·4DMSO (3), [Pb(II)(L(iodo))NO3] (4), and [Sn(IV)(L(iodo))Cl3] (5). Species 1-5 are thoroughly characterized by spectroscopic and spectrometric methods, as well as by elemental analysis. X-ray crystallography results for complex 3 indicate the presence of Hg(II) ion hexacoordinated to two facially oriented [NN'O] ligands, whereas for complex 5 an Sn(IV) ion chelates to one deprotonated ligand and three chlorido coligands. The toxicity of species 1-5 is tested against transformed human prostate epithelial cells CRL2221 and we observe that the five complexes demonstrate high levels of cell growth inhibition in a dose-dependent manner. In order to evaluate the relationship between these species and the proteasome, we test 1-5 against purified 20S, CRL2221 cell extracts, and intact cells, followed by the measurement of the percent chymotrypsin-like activity inhibition levels. Results suggest a good correlation between the toxicity of [Hg(II)(L(iodo))2]·4DMSO (3) and proteasome inhibition.
本文报道了五种金属配合物的合成，这些配合物与 [NN'O] 配体 HL(iodo)（2,4-二碘-6-((吡啶-2-基甲基氨基)甲基)苯酚）配位，即 [Al(III)(L(iodo))2]ClO4（1）、[Cd(II)(L(iodo))Cl]·H2O（2）、[Hg(II)(L(iodo))2]·4DMSO（3）、[Pb(II)(L(iodo))NO3]（4）和 [Sn(IV)(L(iodo))Cl3]（5）。通过光谱和光谱法以及元素分析对 1-5 种物质进行了彻底的表征。配合物 3 的 X 射线晶体学结果表明，Hg(II) 离子六配位与两个面向面的 [NN'O] 配体，而对于配合物 5，Sn(IV) 离子螯合到一个去质子化的配体和三个氯代配位体。我们测试了 1-5 种物质对转化的人前列腺上皮细胞 CRL2221 的毒性，发现这五种物质在剂量依赖性方式下表现出高水平的细胞生长抑制。为了评估这些物质与蛋白酶体之间的关系，我们测试了 1-5 种物质对纯化的 20S、CRL2221 细胞提取物和完整细胞的抑制作用，然后测量糜蛋白酶样活性抑制水平的百分比。结果表明，[Hg(II)(L(iodo))2]·4DMSO（3）的毒性与蛋白酶体抑制之间存在良好的相关性。
