In silico profiling, molecular docking, and RMSD prediction of novel chalcone-schiff base hybrid derivatives as HDAC2 inhibitors

Abstract

Purpose: To investigate the pharmacokinetic properties and binding affinities of a series of chalcone-Schiff base hybrid derivatives.Methods: The pharmacokinetic properties and binding affinities of a series of chalcone-Schiff base hybrid derivatives (compounds I - XI) for HDAC2 enzyme were evaluated using computational techniques (SwissADME wizard and Schrödinger software).Results: All investigated compounds were predicted to exhibit high gastrointestinal absorption and to comply with drug-likeness parameters, such as Lipinski's rule. The compounds (I - XI) displayed comparable binding interactions with the reference ligand (SAHA), particularly Zn2+ coordination. Compounds I, II, III, V, VII (no substitution, ortho OH, para OH, para NO2, and para-Cl substitutions) showed higher binding affinities in kcal/mol with the active site of HDAC2 (-10.330, -10.852, -10.508, -10.282, and -9.811) compared with SAHA (-9.609).Conclusion: Compounds I - XI showed favorable pharmacokinetic properties, characterized by high predicted gastrointestinal absorption and compliance with Lipinski's drug-likeness criteria, suggesting potential suitability as active drug candidates.