Hydroxyl Ketone-Based Histone Deacetylase Inhibitors To Gain Insight into Class I HDAC Selectivity versus That of HDAC6
| Autor: | Claudia A. Simões-Pires, Yung-Sing Wong, Mohamed Dit Mady Traoré, Vincent Zwick, Sharon Wein, Muriel Cuendet, Marjorie Maynadier, Mark E. Issa, Alessandra Nurisso, Henri Vial, Hélène Jamet |
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| Přispěvatelé: | Université des Sciences, des Techniques et des Technologies de Bamako (USTTB), School of Pharmaceutical Sciences, University of Geneva [Switzerland]-Université de Lausanne (UNIL), Dynamique des interactions membranaires normales et pathologiques (DIMNP), Centre National de la Recherche Scientifique (CNRS)-Université de Montpellier (UM)-Université Montpellier 2 - Sciences et Techniques (UM2)-Université Montpellier 1 (UM1), Département de Chimie Moléculaire - Chimie Inorganique Redox Biomimétique (DCM - CIRE ), Département de Chimie Moléculaire (DCM), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019])-Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]), Département de pharmacochimie moléculaire (DPM ), Institut de Chimie du CNRS (INC)-Centre National de la Recherche Scientifique (CNRS)-Université Grenoble Alpes [2016-2019] (UGA [2016-2019]) |
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Gene isoform Ketone Molecular model Stereochemistry General Chemical Engineering 01 natural sciences Article lcsh:Chemistry 03 medical and health sciences [CHIM]Chemical Sciences ComputingMilieux_MISCELLANEOUS chemistry.chemical_classification ddc:615 010405 organic chemistry Chemistry General Chemistry HDAC6 HDAC1 3. Good health 0104 chemical sciences 030104 developmental biology lcsh:QD1-999 Histone deacetylase Selectivity Linker |
| Zdroj: | ACSOmega ACS Omega ACS Omega, Vol. 2, No 4 (2017) pp. 1550-1562 ACS Omega, Vol 2, Iss 4, Pp 1550-1562 (2017) ACS Omega, ACS Publications, 2017, 2 (4), pp.1550-1562. ⟨10.1021/acsomega.6b00481⟩ |
| ISSN: | 2470-1343 |
| Popis: | Little is known about the biological and structural features that govern the isoform selectivity for class I histone deacetylases (HDACs) over HDAC6. In addition to that for known inhibitors, like benzamides, psammaplin A, and cyclodepsipeptide-derived thiols, selectivity was also observed for naturally occurring cyclopeptide HDAC inhibitors with an aliphatic flexible linker and ketonelike zinc-binding group (ZBG). The present study reports that this isoform selectivity is mainly due to the linker and ZBG, as replacement of the cyclopeptide cap region by a simple aniline retained class I HDAC isoform selectivity toward HDAC6 in enzymatic assays. The best cyclopeptide-free analogues preserved efficacy against Plasmodium falciparum and cancer cell lines. Molecular modeling provided hypotheses to explain this selectivity and suggests different behaviors of the flexible linker on HDAC1 and HDAC6 pockets, which may influence, on the basis of the strength of the ZBG, its coordination with the zinc ion. |
| Databáze: | OpenAIRE |
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