Design, Synthesis, and Pharmacological Evaluation of PiperazineHydrazide Derivatives as Potential CNS-Active Antidepressants: MAO-A Inhibition and In Silico Docking Studies on Protein 2BXR and N1 Neuraminidase (PDB 2HU4) for Alzheimer's Disease.

Since piperazine-substituted oxadiazoles have the potential to be kinase inhibitors, antibacterial agents, and medications that target the central nervous system (CNS), their synthesis and evaluation have attracted a lot of attention. In this work, six novel piperazine-oxadiazole derivatives (VSM 1–VSM 6) are designed, synthesised, and biologically evaluated. The compounds were created via condensation processes, hydrazinolysis, and nucleophilic substitution, producing stable heterocyclic structures. Extensive molecular docking studies and spectrum analysis (IR, NMR) were conducted, and in silico predictions suggested promising drug-like qualities. The substances demonstrated minimal toxicity, high oral bioavailability, and blood-brain barrier (BBB) penetration. Furthermore, every drug exhibited favourable pharmacokinetic profiles and passed Lipinski's rule of five. Strong binding affinities to the hMAO-A enzyme were found by docking tests; VSM 3 and VSM 6 had the highest affinities, indicating possible antidepressant action. At dosages of 20–30 mg/kg, VSM 3 and VSM 6 dramatically decreased immobility time, according to biological tests such as the Forced Swim Test (FST) and Tail Suspension Test (TST), which furMolecular docking, blood-brain barrier, forced swimming test, antidepressant, piperazine-substituted oxadiazoles, and drug-like characteristicsther supports their antidepressant-like effects. These results underscore the potential of the compounds to treat depression and point to the need for further study to optimise their safety and effectiveness profiles. Additionally, VSM 2 and VSM 4 demonstrated strong binding affinities to N1 Neuraminidase, indicating potential uses in Alzheimer's disease. The potential of piperazine-substituted oxadiazoles as a treatment for CNS illnesses, including mood disorders and neurodegenerative diseases, is highlighted by this study. [ABSTRACT FROM AUTHOR]