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...
| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
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MDPI AG
2021-06-01
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| Series: | Molecules |
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| Online Access: | https://www.mdpi.com/1420-3049/26/13/3974 |
| _version_ | 1797528403975340032 |
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| author | A. Daryl Ariawan Flora Mansour Nicole Richardson Mohan Bhadbhade Junming Ho Luke Hunter |
| author_facet | A. Daryl Ariawan Flora Mansour Nicole Richardson Mohan Bhadbhade Junming Ho Luke Hunter |
| author_sort | A. Daryl Ariawan |
| collection | DOAJ |
| 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. |
| first_indexed | 2024-03-10T09:57:52Z |
| format | Article |
| id | doaj.art-838aa2a1009f47e28833fcd3005337e6 |
| institution | Directory Open Access Journal |
| issn | 1420-3049 |
| language | English |
| last_indexed | 2024-03-10T09:57:52Z |
| publishDate | 2021-06-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Molecules |
| spelling | doaj.art-838aa2a1009f47e28833fcd3005337e62023-11-22T02:12:22ZengMDPI AGMolecules1420-30492021-06-012613397410.3390/molecules26133974The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase InhibitorsA. Daryl Ariawan0Flora Mansour1Nicole Richardson2Mohan Bhadbhade3Junming Ho4Luke Hunter5School of Chemistry, UNSW Sydney, Sydney, NSW 2052, AustraliaSchool of Chemistry, UNSW Sydney, Sydney, NSW 2052, AustraliaSchool of Chemistry, UNSW Sydney, Sydney, NSW 2052, AustraliaMark Wainwright Analytical Centre, UNSW Sydney, Sydney, NSW 2052, AustraliaSchool of Chemistry, UNSW Sydney, Sydney, NSW 2052, AustraliaSchool of Chemistry, UNSW Sydney, Sydney, NSW 2052, AustraliaHistone 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.https://www.mdpi.com/1420-3049/26/13/3974SAHAScriptaidstereoselective fluorinationHDAC |
| spellingShingle | A. Daryl Ariawan Flora Mansour Nicole Richardson Mohan Bhadbhade Junming Ho Luke Hunter The Effect of Vicinal Difluorination on the Conformation and Potency of Histone Deacetylase Inhibitors Molecules SAHA Scriptaid stereoselective fluorination HDAC |
| 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 | SAHA Scriptaid stereoselective fluorination HDAC |
| url | https://www.mdpi.com/1420-3049/26/13/3974 |
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