Journal
NATURE CHEMISTRY
Volume 10, Issue 3, Pages 347-354Publisher
NATURE PUBLISHING GROUP
DOI: 10.1038/NCHEM.2918
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Funding
- European Research Council [247450, 324594]
- Science City (Advantage West Midlands)
- Science City (European Regional Development Fund)
- Warwick Collaborative Postgraduate Research Scholarship
- Bruker Daltonics
- Engineering and Physical Research Council/Cancer Research UK [C53561/A19933]
- EU COST Action [CM1105]
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Catalytic anticancer metallodrugs active at low doses could minimize side-effects, introduce novel mechanisms of action that combat resistance and widen the spectrum of anticancer-drug activity. Here we use highly stable chiral half-sandwich organometallic Os(II) arene sulfonyl diamine complexes, [Os(arene)(TsDPEN)] (TsDPEN, N-(p-toluenesulfonyl)-1,2-diphenylethylenediamine), to achieve a highly enantioselective reduction of pyruvate, a key intermediate in metabolic pathways. Reduction is shown both in aqueous model systems and in human cancer cells, with non-toxic concentrations of sodium formate used as a hydride source. The catalytic mechanism generates selectivity towards ovarian cancer cells versus non-cancerous fibroblasts (both ovarian and lung), which are commonly used as models of healthy proliferating cells. The formate precursor N-formylmethionine was explored as an alternative to formate in PC3 prostate cancer cells, which are known to overexpress a deformylase enzyme. Transfer-hydrogenation catalysts that generate reductive stress in cancer cells offer a new approach to cancer therapy.
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