Zhang Jingwen, Pitto-Barry Anaïs, Shang Lijun, Barry Nicolas P E
School of Chemistry and Biosciences, University of Bradford, Bradford BD7 1DP, UK.
R Soc Open Sci. 2017 Nov 29;4(11):170786. doi: 10.1098/rsos.170786. eCollection 2017 Nov.
We report an evaluation of the cytotoxicity of a series of electron-deficient (16-electron) half-sandwich precious metal complexes of ruthenium, osmium and iridium ([Os/Ru(--cymene)(1,2-dicarba--dodecarborane-1,2-dithiolato)] (), [Ir(-pentamethylcyclopentadiene)(1,2-dicarba--dodecarborane-1,2-dithiolato)] (), [Os/Ru(--cymene)(benzene-1,2-dithiolato)] () and [Ir(-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] ()) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes and were found to be non-cytotoxic. The anti-inflammatory activity of was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as the stimulus. All metal complexes were shown to exhibit dose-dependent inhibitory effects on LPS-induced NO production on both cell lines. Remarkably, the two iridium complexes and trigger a full anti-inflammatory response against LPS-induced NO production, which opens up new avenues for the development of non-cytotoxic anti-inflammatory drug candidates with distinct structures and solution chemistry from that of organic drugs, and as such with potential novel mechanisms of action.
我们报告了对一系列缺电子（16电子）的钌、锇和铱半夹心贵金属配合物（[Os/Ru（对异丙基苯）（1,2-二碳-十二硼烷-1,2-二硫醇盐）]（）、[Ir（五甲基环戊二烯基）（1,2-二碳-十二硼烷-1,2-二硫醇盐）]（）、[Os/Ru（对异丙基苯）（苯-1,2-二硫醇盐）]（）和[Ir（五甲基环戊二烯基）（苯-1,2-二硫醇盐）]（））对RAW 264.7小鼠巨噬细胞和MRC-5成纤维细胞的细胞毒性的评估。发现配合物和无细胞毒性。以细菌内毒素脂多糖（LPS）为刺激物，在两种细胞系中诱导一氧化氮（NO）产生和炎症反应后，评估了的抗炎活性。所有金属配合物均显示出对两种细胞系中LPS诱导的NO产生具有剂量依赖性抑制作用。值得注意的是，两种铱配合物和引发了针对LPS诱导的NO产生的完全抗炎反应，这为开发具有与有机药物不同的结构和溶液化学性质、因而具有潜在新作用机制的无细胞毒性抗炎候选药物开辟了新途径。
