Zhang Chen, Bourgeade Delmas Sandra, Fernández Álvarez Álvaro, Valentin Alexis, Hemmert Catherine, Gornitzka Heinz
CNRS, LCC (Laboratoire de Chimie de Coordination), 205 route de Narbonne, BP 44099, F-31077 Toulouse Cedex 4, France; Université de Toulouse, UPS, INPT, F-31077 Toulouse Cedex 4, France.
UMR 152 PHARMA-DEV, Université de Toulouse, IRD, UPS, France.
Eur J Med Chem. 2018 Jan 1;143:1635-1643. doi: 10.1016/j.ejmech.2017.10.060. Epub 2017 Oct 24.
A series of five new mononuclear neutral gold(I) complexes containing N-heterocyclic carbenes (NHCs) was synthesized and fully characterized by spectroscopic methods. The X-ray structures of four complexes are presented. These gold(I) complexes together with four other neutral gold(I)-NHC complexes previously described were evaluated in vitro against Leishmania infantum promastigotes and axenic amastigotes. Moreover, their cytotoxicity was assessed on the murine macrophages J774A.1. Except one complex (10), eight gold(I)-NHC-Cl complexes show potent activity against the pathological relevant form of L. infantum amastigote with IC in the low micromolar and submicromolar range and five of them exhibit a SI close to 10. The lead-complex 11 displays a very high and selective activity (IC = 190 nM, SI = 40.29) and constitutes the best promising gold(I)-based drug of this series.
合成了一系列五个含氮杂环卡宾（NHCs）的新型单核中性金（I）配合物，并通过光谱方法对其进行了全面表征。给出了四个配合物的X射线结构。将这些金（I）配合物与先前描述的其他四个中性金（I）-NHC配合物一起在体外针对婴儿利什曼原虫前鞭毛体和无菌无鞭毛体进行了评估。此外，还评估了它们对小鼠巨噬细胞J774A.1的细胞毒性。除了一种配合物（10）外，八个金（I）-NHC-Cl配合物对婴儿利什曼原虫无鞭毛体的病理相关形式显示出强效活性，IC处于低微摩尔和亚微摩尔范围内，其中五个的SI接近10。先导配合物11表现出非常高的选择性活性（IC = 190 nM，SI = 40.29），是该系列中最有前景的基于金（I）的药物。
