Department of Organic Chemistry I, Faculty of Pharmacy, University of Basque Country (UPV/EHU), Vitoria-Gasteiz, Spain.
Dalton Trans. 2020 Jun 21;49(23):7852-7861. doi: 10.1039/d0dt01467b. Epub 2020 May 28.
This work describes the synthesis of the gold(i) complexes of phosphine sulphides. The formation of these new derivatives has been confirmed by X-ray crystallography. The coordination of gold(i) with the sulphur atom of the phosphine sulphides favors the inhibition of topoisomerase I as well as a high cytotoxicity of the gold(i)-complexed compounds against the cancer line A549 with IC values in the nanomolar range and IC values below 5 μM against the SKOV3 cell line. It should be noted that the cytotoxicities observed for the new gold(i) complexes are higher than those observed for phosphine sulphide ligands before binding to gold. Furthermore, the results also indicate that the presence of a nitrogenated heterocycle, such as tetrahydroquinoline or quinoline, is also necessary for the TopI inhibition to be maintained. In addition, no toxicity was observed when the non-cancerous lung fibroblast cell line (MRC5) was treated with the new phosphine sulphide gold(i) complexes prepared.
本工作描述了膦硫醚的金（i）配合物的合成。通过 X 射线晶体学证实了这些新衍生物的形成。金（i）与膦硫醚的硫原子的配位有利于拓扑异构酶 I 的抑制，以及金（i）配合物对肺癌细胞系 A549 的高细胞毒性，IC 值在纳摩尔范围内，对 SKOV3 细胞系的 IC 值低于 5 μM。值得注意的是，与配体结合前的膦硫醚相比，新的金（i）配合物的细胞毒性更高。此外，结果还表明，氮杂环如四氢喹啉或喹啉的存在对于维持 TopI 抑制也是必要的。此外，当用新的膦硫醚金（i）配合物处理非癌细胞系（MRC5）时，未观察到毒性。
