The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11

Andreas Stahl Madsen, Helle M. E. Kristensen, Gyrithe Lanz, Christian Adam Olsen

Research output: Contribution to journalJournal articleResearchpeer-review


Histone deacetylases (HDACs) have the ability to cleave the acetyl groups of ε‐N‐acetylated lysine residues in a variety of proteins. Given that human cells contain thousands of different acetylated lysine residues, HDACS may regulate a wide variety of processes including some implicated in conditions such as cancer and neurodegenerative disorders. Herein we report the synthesis and in vitro biochemical profiling of a series of compounds, including known inhibitors as well as novel chemotypes, that incorporate putative new zinc binding domains. By evaluating the compound collection against all 11 recombinant human HDACs, we found that the trifluoromethyl ketone functionality provides potent inhibition of all four subclasses of the Zn2+‐dependent HDACs. Potent inhibition was observed with two different scaffolds, demonstrating the efficiency of the trifluoromethyl ketone moiety as a zinc binding motif. Interestingly, we also identified silanediol as a zinc binding group with potential for future development of non‐hydroxamate class I and class IIb HDAC inhibitors.
Original languageEnglish
Issue number3
Pages (from-to)614-626
Publication statusPublished - 2014


Dive into the research topics of 'The Effect of Various Zinc Binding Groups on Inhibition of Histone Deacetylases 1–11'. Together they form a unique fingerprint.

Cite this