Histone deacetylase (HDAC) has a critical function in regulating gene expression. The inhibition of HDAC has developed as an interesting anticancer research area that targets biological processes such as cell cycle, apoptosis, and cell differentiation. In this study, an HDAC inhibitor that is available commercially, suberoyl anilide hydroxamic acid (SAHA), has been modified to improve its efficacy and reduce the side effects of the compound. Hydrophobic cap and zinc‐binding group of these compounds were substituted with boron‐based compounds, whereas the linker region was substituted with p‐aminobenzoic acid. The molecular docking analysis resulted in 8 ligands with ΔG_binding value more negative than the standards, SAHA and trichostatin A (TSA). That ligands were analyzed based on the nature of QSAR, pharmacological properties, and ADME‐Tox. It is conducted to obtain a potent inhibitor of HDAC class II Homo sapiens. The screening process result gave one best ligand, Nova2 (513246‐99‐6), which was then further studied by molecular dynamics simulations.