The first examples of RuII and RhIII piano‐stool complex histone deacetylase (HDAC) inhibitors are presented. The novel complexes have antiproliferative activity against H460 non‐small‐cell lung carcinoma cells that is comparable to the clinically used HDAC inhibitor suberoylanilide hydroxamic acid (SAHA). Strong evidence for HDAC inhibition as a primary mechanism of action is provided. The complexes reported here represent an important step towards the design of highly active and selective HDAC inhibitors.

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