Next Article in Journal
Three-Component Suzuki–Knoevenagel Synthesis of Merocyanine Libraries and Correlation Analyses of Their Oxidation Potentials and Optical Band Gaps
Next Article in Special Issue
Carbonic Anhydrase Inhibitors and Epilepsy: State of the Art and Future Perspectives
Previous Article in Journal
Abietane Diterpenoids from the Hairy Roots of Salvia corrugata
Previous Article in Special Issue
Identification of Broad-Spectrum MMP Inhibitors by Virtual Screening
 
 
Review

Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases

Department of Chemical Engineering and Biotechnology, University of Applied Sciences Darmstadt, Haardtring 100, 64295 Darmstadt, Germany
*
Author to whom correspondence should be addressed.
Academic Editor: Elisa Nuti
Molecules 2021, 26(17), 5151; https://doi.org/10.3390/molecules26175151
Received: 5 July 2021 / Revised: 22 August 2021 / Accepted: 24 August 2021 / Published: 25 August 2021
(This article belongs to the Special Issue Metalloenzyme Inhibitors and Activators II)
Histone deacetylases (HDACs) remove acetyl groups from acetylated lysine residues and have a large variety of substrates and interaction partners. Therefore, it is not surprising that HDACs are involved in many diseases. Most inhibitors of zinc-dependent HDACs (HDACis) including approved drugs contain a hydroxamate as a zinc-binding group (ZBG), which is by far the biggest contributor to affinity, while chemical variation of the residual molecule is exploited to create more or less selectivity against HDAC isozymes or other metalloproteins. Hydroxamates have a propensity for nonspecificity and have recently come under considerable suspicion because of potential mutagenicity. Therefore, there are significant concerns when applying hydroxamate-containing compounds as therapeutics in chronic diseases beyond oncology due to unwanted toxic side effects. In the last years, several alternative ZBGs have been developed, which can replace the critical hydroxamate group in HDACis, while preserving high potency. Moreover, these compounds can be developed into highly selective inhibitors. This review aims at providing an overview of the progress in the field of non-hydroxamic HDACis in the time period from 2015 to present. Formally, ZBGs are clustered according to their binding mode and structural similarity to provide qualitative assessments and predictions based on available structural information. View Full-Text
Keywords: histone deacetylase (HDAC); histone deacetylase inhibitors (HDACis); zinc-binding group (ZBG); non-hydroxamate histone deacetylase (HDAC); histone deacetylase inhibitors (HDACis); zinc-binding group (ZBG); non-hydroxamate
Show Figures

Figure 1

MDPI and ACS Style

Frühauf, A.; Meyer-Almes, F.-J. Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases. Molecules 2021, 26, 5151. https://doi.org/10.3390/molecules26175151

AMA Style

Frühauf A, Meyer-Almes F-J. Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases. Molecules. 2021; 26(17):5151. https://doi.org/10.3390/molecules26175151

Chicago/Turabian Style

Frühauf, Anton, and Franz-Josef Meyer-Almes. 2021. "Non-Hydroxamate Zinc-Binding Groups as Warheads for Histone Deacetylases" Molecules 26, no. 17: 5151. https://doi.org/10.3390/molecules26175151

Find Other Styles
Note that from the first issue of 2016, MDPI journals use article numbers instead of page numbers. See further details here.

Article Access Map by Country/Region

1
Back to TopTop