Background: Histone deacetylases (HDACs) emerged as important epigenetic regulators
of gene expression.
Method: In order to identify potential positron emission tomography (PET) tracers for imaging
HDACs, we evaluated in vitro and in cellulo activities of some compounds that were reported as
potent HDAC2-selective inhibitors. We observed marked differences between reported activity
values and the values obtained in our assays for some of the compounds. To understand the structural
basis of the activity of some of these inhibitors, we also performed molecular docking studies to
understand their interaction patterns and binding modes with HDAC2.
Results and Conclusion: We observed the low affinity compounds 4, 6 and 7 did not showed equal
number of key π-π interactions and hydrogen bonding when compared to high affinity compounds,
and could be the possible reason for poor inhibition as reflected in in vitro assays. These preliminary
experimental and computational results will help to interpret the HDAC affinity values of these key
compounds with caution.