New halo-enaminones as potential CNS drugs: Synthesis, characterization, DFT, NLO, molecular docking, and ADMET analysis

Some new halo-enaminones (2b-2g) of (Z)-1-(((2-acetylphenyl)amino)methylene)naphthalen-2(1H)-one (2a) were successfully synthesized in a very good yield. They were characterized by spectroscopic techniques. The single crystal XRD analysis confirmed the structure, stereochemistry, and hydrogen bond interactions of the synthesized enaminones. Density Functional Theory (DFT) and Time-Dependent Density Functional Theory (TDDFT) were employed to study theoretical attributes such as Structural analysis, Natural Bond Order analysis (NBO), Frontier molecular Orbital Analysis (FMO), Global and local reactivity descriptors, Molecular Electrostatic Potential (MEP) analysis, Absorption, Emission and Non-Linear Optical (NLO) properties. Molecular docking analysis revealed that all these compounds had an excellent binding energy of ∼ -12 kcal/mol, with the human Sirtuin 2 (SIRT2) protein (PDB ID: 5Y5N), which is predominantly expressed in the brain. In addition, ADMET analysis revealed that all of them have drug-like properties, Blood Brain Barrier (BBB) permeable, and are not P–Glycoprotein substrates, implying that they are potential Central Nervous System (CNS) drugs.