Chiral Mercaptoacetamides Display Enantioselective Inhibition of Histone Deacetylase 6 and Exhibit Neuroprotection in Cortical Neuron Models of Oxidative Stress
Citations Over TimeTop 14% of 2012 papers
Abstract
Abstract Mercaptoacetamide‐based ligands have been designed as a new class of histone deacetylase (HDAC) inhibitors for possible use in the treatment of neurodegenerative diseases. The thiol group of these compounds provides a key binding element for interaction with the catalytic zinc ion, and thus differs from the more typically employed hydroxamic acid based zinc binding groups. Herein we disclose the chemistry and biology of some substituted mercaptoacetamides with the intention of increasing HDAC6 isoform selectivity while maintaining potency similar to their hydroxamic acid analogues. The introduction of a stereocenter α to the thiol group was found to have a considerable impact on HDAC inhibitor potency. These new compounds were also profiled for their therapeutic potential in an in vitro model of stress‐induced neuronal injury and were found to act as nontoxic neuroprotective agents.
Related Papers
- → 3-Hydroxypyridin-2-thione as Novel Zinc Binding Group for Selective Histone Deacetylase Inhibition(2013)72 cited
- → Design, synthesis and preliminary bioactivity studies of 1,3,4-thiadiazole hydroxamic acid derivatives as novel histone deacetylase inhibitors(2012)52 cited
- → Mercaptoamide-based non-hydroxamic acid type histone deacetylase inhibitors(2005)35 cited
- → Hybrids from Farnesylthiosalicylic Acid and Hydroxamic Acid as Dual Ras‐Related Signaling and Histone Deacetylase (HDAC) Inhibitors: Design, Synthesis and Biological Evaluation(2015)29 cited
- → α-Mercaptoketone based histone deacetylase inhibitors(2008)7 cited