The effect of vicinal difluorination on the conformation and potency of histone deacetylase inhibitors

A. Daryl Ariawan; Flora Mansour; Nicole Richardson; Mohan Bhadbhade; Junming Ho; Luke Hunter

doi:10.3390/molecules26133974

The effect of vicinal difluorination on the conformation and potency of histone deacetylase inhibitors

A. Daryl Ariawan, Flora Mansour, Nicole Richardson, Mohan Bhadbhade, Junming Ho, Luke Hunter^*

^*Corresponding author for this work

Research output: Contribution to journal › Article › peer-review

4 Citations (Scopus)

54 Downloads (Pure)

Abstract

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.

Original language	English
Article number	3974
Pages (from-to)	1-17
Number of pages	17
Journal	Molecules
Volume	26
Issue number	13
DOIs	https://doi.org/10.3390/molecules26133974
Publication status	Published - 29 Jun 2021
Externally published	Yes

Bibliographical note

Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

Keywords

SAHA
Scriptaid
stereoselective fluorination
HDAC
Stereoselective fluorination

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10.3390/molecules26133974Licence: CC BY

Publisher version (open access)Final published version, 7.58 MBLicence: CC BY

Cite this

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AU - Richardson, Nicole

AU - Bhadbhade, Mohan

AU - Ho, Junming

AU - Hunter, Luke

N1 - Copyright the Author(s) 2021. Version archived for private and non-commercial use with the permission of the author/s and according to publisher conditions. For further rights please contact the publisher.

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N2 - 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.

AB - 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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The effect of vicinal difluorination on the conformation and potency of histone deacetylase inhibitors

Abstract

Bibliographical note

Keywords

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