학술논문
PotentHistone Deacetylase Inhibitors Derived from4-(Aminomethyl)-N-hydroxybenzamidewith High Selectivity for the HDAC6 Isoform.
Document Type
Article
Author
Source
Subject
*HISTONE deacetylase inhibitors
*BENZAMIDE
*HETEROCYCLIC compounds
*TETRAHYDROISOQUINOLINES
*CHEMICAL synthesis
*BENZYLIC group
*BINDING sites
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Language
ISSN
0022-2623
Abstract
A screen for HDAC6 inhibitors identifiedacyl derivatives of 4-(aminomethyl)-N-hydroxybenzamideas potent leads with unexpected selectivityover the other subtypes. We designed and synthesized constrained heterocyclicanalogues such as tetrahydroisoquinolines that show further enhancedHDAC6 selectivity and inhibitory activity in cellular assays. Selectivitymay be attributed to the benzylic spacer more effectively accessingthe wider channel of HDAC6 compared to other HDAC subtypes as wellas hydrophobic capping groups interacting with the protein surfacenear the rim of the active site. [ABSTRACT FROM AUTHOR]