Online citations, reference lists, and bibliographies.

The Effect Of Various Zinc Binding Groups On Inhibition Of Histone Deacetylases 1-11.

Andreas S. Madsen, Helle M. E. Kristensen, Gyrithe Lanz, Christian A. Olsen
Published 2014 · Medicine, Chemistry
Cite This
Download PDF
Analyze on Scholarcy
Share
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 Zn(2+) -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.



This paper is referenced by
10.3390/md18040179
Assessment of the Allelochemical Activity and Biochemical Profile of Different Phenotypes of Picocyanobacteria from the Genus Synechococcus
Zofia Konarzewska (2020)
10.1016/j.chembiol.2018.04.007
Histone Deacetylase 11 Is an ε-N-Myristoyllysine Hydrolase.
Carlos Moreno-Yruela (2018)
10.1002/anie.201701026
Inhibiting Polysulfide Shuttle in Lithium-Sulfur Batteries through Low-Ion-Pairing Salts and a Triflamide Solvent.
Abhinandan Shyamsunder (2017)
10.4274/tjps.75047
Histone Deacetylase Inhibitors: A Prospect in Drug Discovery
Rakesh Yadav (2019)
10.3390/molecules23051166
Clinically Applicable Inhibitors Impacting Genome Stability
Anu Prakash (2018)
10.2147/DDDT.S110997
Novel glyoxalase-I inhibitors possessing a “zinc-binding feature” as potential anticancer agents
Qosay A Al-Balas (2016)
10.1016/j.cbpa.2016.12.011
Developing drugs targeting transition metal homeostasis.
Claire M Weekley (2017)
10.1515/hsz-2018-0363
Kinetically selective and potent inhibitors of HDAC8
Markus Schweipert (2019)
10.1002/chem.201605140
A Fluorescence-Lifetime-Based Binding Assay for Class IIa Histone Deacetylases.
Christian Stephan Meyners (2017)
10.1002/9783527809257.CH7
Inhibitors of the Zinc‐Dependent Histone Deacetylases
Helle M. E. Kristensen (2019)
10.1021/acs.jmedchem.7b00718
Quest for Novel Chemical Entities through Incorporation of Silicon in Drug Scaffolds.
Remya Ramesh (2018)
Development of a UV-Cleavable Protecting Group for Hydroxylamines, Synthesis of a StructurallyWide Variety of Hydroxamic Acids, and Identification of Histone Deacetylase Inhibitors
Kim T. Mortensen (2017)
10.17179/excli2017-208
Microwave-assisted synthesis and antitumor evaluation of a new series of thiazolylcoumarin derivatives
Moustafa T Gabr (2017)
10.1039/c7ob02862h
Convenient, functional group-tolerant, transition metal-free synthesis of aryl and heteroaryl trifluoromethyl ketones with the use of methyl trifluoroacetate.
Kazumasa Funabiki (2018)
10.1002/open.201800117
SAHAquines, Novel Hybrids Based on SAHA and Primaquine Motifs, as Potential Cytostatic and Antiplasmodial Agents
Maja Beus (2018)
10.4155/fmc-2016-0193
Progress in the medicinal chemistry of silicon: C/Si exchange and beyond.
Shinya Fujii (2017)
10.1021/jm500984b
Exploring the Influence of the Protein Environment on Metal-Binding Pharmacophores
David P. Martin (2014)
Epigenetics - Histone Deacetylase (HDAC) Inhibitors
Christian A. Olsen (2014)
10.1021/acs.biochem.7b00725
Chemical Editing of Macrocyclic Natural Products and Kinetic Profiling Reveal Slow, Tight-Binding Histone Deacetylase Inhibitors with Picomolar Affinities.
Betuel Kitir (2017)
10.3390/molecules20033898
Histone Deacetylase Inhibitors in Clinical Studies as Templates for New Anticancer Agents
Madhusoodanan Mottamal (2015)
10.1101/211839
Histone Deacetylase 11 is an ε-N-Myristoyllysine Hydrolase
Carlos Moreno-Yruela (2017)
10.1016/J.TET.2018.12.011
Phenylethylene glycol-derived LpxC inhibitors with diverse Zn2+-binding groups
M. Galster (2019)
Semantic Scholar Logo Some data provided by SemanticScholar