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Anti-inflammatory activity of electron-deficient organometallics
Zhang, Jingwen Pitto-Barry, Anaïs Shang, Lijun Barry, Nicolas P.E.
Zhang, Jingwen
Pitto-Barry, Anaïs
Shang, Lijun
Barry, Nicolas P.E.
Publication Date
2017
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©2017 The Authors. Published by the Royal Society under the terms of the Creative Commons Attribution License http://creativecommons.org/licenses/by/4.0/, which permits unrestricted use, provided the original author and source are credited.
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openAccess
Accepted for publication
2017-10-26
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Abstract
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-pcymene)(
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 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 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.
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Citation
Zhang J, Pitto-Barry A, Shang L et al (2017) Anti-inflammatory activity of electrondeficient
organometallics. Royal Society Open Science. 4: 170786.
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Article