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姜黄素类似物及其铜配合物潜在药理活性的体外研究

In vitro study on potential pharmacological activity of curcumin analogues and their copper complexes.

作者信息

Ferrari Erika, Benassi Rois, Saladini Monica, Orteca Giulia, Gazova Zuzana, Siposova Katarina

机构信息

Department of Chemical and Geological Sciences, University of Modena and Reggio Emilia, Modena, Italy.

Department of Biophysics, Institute of Experimental Physics Slovak Academy of Sciences, Kosice, Slovakia.

出版信息

Chem Biol Drug Des. 2017 Mar;89(3):411-419. doi: 10.1111/cbdd.12847. Epub 2016 Sep 23.

Abstract

Curcumin and its derivatives have attracted great interest in the prevention and treatment of Alzheimer's disease, thanks both to the ability to hinder the formation of amyloid-beta (Aβ) aggregates and the ability to bind Cu (II) ion. In this article, we explore the ability of curcumin derivatives of K2T series to affect amyloid Aβ aggregation. These derivatives were obtained by introducing the t-butyl ester group through a methylenic spacer on the central carbon atom of the β-diketo moiety of curcumin frame. The studied curcuminoids were demonstrated to inhibit Aβ fibrillization at substoichiometric concentrations with IC value near that of curcumin. In addition, the antioxidant properties and DNA interaction of their Cu(II) complexes is evaluated. The structure of Cu(II)-K2T31 complex is also proposed on the basis of DFT calculation.

摘要

姜黄素及其衍生物因其能够抑制β-淀粉样蛋白(Aβ)聚集体的形成以及结合铜(II)离子的能力,在阿尔茨海默病的预防和治疗方面引起了极大的关注。在本文中,我们探究了K2T系列姜黄素衍生物影响淀粉样Aβ聚集的能力。这些衍生物是通过在姜黄素骨架的β-二酮部分的中心碳原子上通过亚甲基间隔引入叔丁酯基团而获得的。研究表明,所研究的姜黄素类化合物在亚化学计量浓度下能够抑制Aβ纤维化,其IC值与姜黄素相近。此外,还评估了它们的铜(II)配合物的抗氧化性能和与DNA的相互作用。基于密度泛函理论(DFT)计算,还提出了铜(II)-K2T31配合物的结构。

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