Department of Chemistry, Wayne State University, Detroit, MI 48202, USA.
Eur J Med Chem. 2009 Nov;44(11):4353-61. doi: 10.1016/j.ejmech.2009.05.019. Epub 2009 May 24.
Selective 20S proteasomal inhibition and apoptosis induction were observed when several lines of cancer cells were treated with a series of copper complexes described as [Cu(L(I))Cl] (1), [Cu(L(I))OAc] (2), and [Cu(HL(I))(L(I))]OAc (3), where HL(I) is the ligand 2,4-diiodo-6-((pyridine-2-ylmethylamino)methyl)phenol. These complexes were synthesized, characterized by means of ESI spectrometry, infrared, UV-visible and EPR spectroscopies, and X-ray diffraction when possible. After full characterization species 1-3 were evaluated for their ability to function as proteasome inhibitors and apoptosis inducers in C4-2B and PC-3 human prostate cancer cells and MCF-10A normal cells. With distinct stoichiometries and protonation states, this series suggests the assignment of species CuL(I) as the minimal pharmacophore needed for proteasomal chymotryspin-like activity inhibition and permits some initial inference of mechanistic information.
当用一系列被描述为 [Cu(L(I))Cl] (1)、[Cu(L(I))OAc] (2) 和 [Cu(HL(I))(L(I))]OAc (3) 的铜配合物处理几种癌细胞系时，观察到选择性的 20S 蛋白酶体抑制和细胞凋亡诱导，其中 HL(I) 是配体 2,4-二碘-6-((吡啶-2-基甲基氨基)甲基)苯酚。这些配合物通过 ESI 光谱、红外、紫外-可见和 EPR 光谱以及 X 射线衍射进行了合成和表征，在可能的情况下。在充分表征后，评估了 1-3 种物质在 C4-2B 和 PC-3 人前列腺癌细胞和 MCF-10A 正常细胞中作为蛋白酶体抑制剂和凋亡诱导剂的能力。由于具有不同的化学计量和质子化状态，该系列表明分配物 [CuL(I)] (+) 是抑制蛋白酶体糜蛋白酶样活性所需的最小药效团，并允许对机制信息进行一些初步推断。
