Design, Synthesis, and In-silico Evaluation of Benzyl oxybenzoate Derivatives as Dual HDAC Inhibitors for Cancer and CNS Disorders

Histone deacetylase (HDAC) inhibitors have garnered attention as possible therapies for disorders affecting the central nervous system (CNS) and cancer. Because HDACs, particularly HDAC1 and HDAC2, are overexpressed in many cancers and govern neurological diseases, they are dual targets for therapeutic interventions. Therefore, this study aims to synthesize benzyl oxybenzoate and use pharmacokinetic analyses and molecular docking to evaluate their potential as HDAC inhibitors. After synthesizing benzoyl oxybenzoate derivatives, their potential as HDAC inhibitors was evaluated by comparing their binding affinity and mechanism to that of SAHA, a well-known HDAC inhibitor, utilizing molecular docking against HDAC2. To forecast pharmacokinetics, the ADME profiles of these substances—such as oral bioavailability and blood-brain barrier (BBB) permeability—were also assessed. A number of synthetic compounds showed promising binding affinities against HDAC2, indicating their potential as HDAC inhibitors. According to the results, the designed compounds that were found may be investigated further as dual-action medications for CNS diseases and cancer.