Design, synthesis and biological evaluation of novel histone deacetylase inhibitors based on virtual screening

Ligand- and structure-based virtual screening methods were employed to identify novel non-hydroxamate histone deacetylase (HDAC) inhibitors. Based on the newly identified hit compound 17a, three series of compounds were synthesized and evaluated for both HDAC1 inhibitory activity and cytotoxicity. Binding modes of representative structures were analyzed using the docking method to explain the observed disparity in HDAC1 inhibitory activities.