Anti-inflammatory activity of electron-deficient organometallics
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KeywordsHalf-sandwich complexes; Carborane; Electron-deficient; Anti-inflammatory; Nitric oxide (NO); RAW 264.7 macrophages; MRC-5 fibroblast
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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(η6-p-cymene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (1/2), [Ir(η5-pentamethylcyclopentadiene)(1,2-dicarba-closo-dodecarborane-1,2-dithiolato)] (3), [Os/Ru(η6-p-cymene)(benzene-1,2-dithiolato)] (4/5), and [Ir(η5-pentamethylcyclopentadiene)(benzene-1,2-dithiolato)] (6)) towards RAW 264.7 murine macrophages and MRC-5 fibroblast cells. Complexes 3 and 6 were found to be non-cytotoxic. The anti-inflammatory activity of 1 – 6 was evaluated in both cell lines after nitric oxide (NO) production and inflammation response induced by bacterial endotoxin lipopolysaccharide (LPS) as 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 3 and 6 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.