The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors

Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the...

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Autores principales: Ariawan, A. Daryl, Mansour, Flora, Richardson, Nicole, Bhadbhade, Mohan, Ho, Junming, Hunter, Luke
Formato: Online Artículo Texto
Lenguaje:English
Publicado: MDPI 2021
Materias:
Article
Acceso en línea:https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271401/
https://www.ncbi.nlm.nih.gov/pubmed/34209791
http://dx.doi.org/10.3390/molecules26133974
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author Ariawan, A. Daryl
Mansour, Flora
Richardson, Nicole
Bhadbhade, Mohan
Ho, Junming
Hunter, Luke
author_facet Ariawan, A. Daryl
Mansour, Flora
Richardson, Nicole
Bhadbhade, Mohan
Ho, Junming
Hunter, Luke
author_sort Ariawan, A. Daryl
collection PubMed
description Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the molecules with specifically positioned fluorine atoms in order to control the molecular conformations. The fluorinated analogs were screened against a panel of 11 HDAC isoforms, and minor differences in isoform selectivity patterns were observed.
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spelling pubmed-82714012021-07-11 The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors Ariawan, A. Daryl Mansour, Flora Richardson, Nicole Bhadbhade, Mohan Ho, Junming Hunter, Luke Molecules Article Histone deacetylase enzymes (HDACs) are potential targets for the treatment of cancer and other diseases, but it is challenging to design isoform-selective agents. In this work, we created new analogs of two established but non-selective HDAC inhibitors. We decorated the central linker chains of the molecules with specifically positioned fluorine atoms in order to control the molecular conformations. The fluorinated analogs were screened against a panel of 11 HDAC isoforms, and minor differences in isoform selectivity patterns were observed. MDPI 2021-06-29 /pmc/articles/PMC8271401/ /pubmed/34209791 http://dx.doi.org/10.3390/molecules26133974 Text en © 2021 by the authors. https://creativecommons.org/licenses/by/4.0/Licensee MDPI, Basel, Switzerland. This article is an open access article distributed under the terms and conditions of the Creative Commons Attribution (CC BY) license (https://creativecommons.org/licenses/by/4.0/).
spellingShingle Article
Ariawan, A. Daryl
Mansour, Flora
Richardson, Nicole
Bhadbhade, Mohan
Ho, Junming
Hunter, Luke
The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors
title The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors
title_full The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors
title_fullStr The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors
title_full_unstemmed The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors
title_short The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors
title_sort effect of vicinal difluorination on the conformation and potency of histone deacetylase inhibitors
topic Article
url https://www.ncbi.nlm.nih.gov/pmc/articles/PMC8271401/
https://www.ncbi.nlm.nih.gov/pubmed/34209791
http://dx.doi.org/10.3390/molecules26133974
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