Synthesis, Computational Analysis, and Pharmacological Evaluation of Novel Schiff Base Hybrids for Anxiolytic and Skeletal Muscle-relaxant Activities

Introduction: Schiff bases are a well-known class of substances with a variety of pharmacological properties, including skeletal muscle relaxant and anxiolytic effects. They are ideal candidates for the development of CNS-active drugs due to their structural adaptability and ability to interact with a range of biological targets. The purpose of this study was to create, synthesize, and describe new Schiff base hybrids and assess their possible skeletal muscle relaxant and anxiolytic effects using pharmacological and computational techniques. Methods: By using condensation reactions between primary amines and substituted aromatic aldehydes, several new Schiff base hybrids were created. FT-IR, ¹H NMR, ¹³C NMR, and mass spectrometry were used for structural elucidation. To evaluate binding affinity with GABA-A and NMDA receptor sites, computational investigations involving molecular docking and ADME profiling were carried out. Validated rodent models were utilized for pharmacological evaluations, including the rotarod and traction tests to assess skeletal muscle relaxation, as well as the elevated plus maze and open-field tests to evaluate anxiolytic activity. Results: The synthesized Schiff base derivatives demonstrated high purity and stability. In accordance with the observed in vivo anxiolytic activity, docking studies demonstrated advantageous binding interactions with the GABA-A receptor. Discussion: Certain compounds exhibited moderate skeletal muscle relaxant activity, without producing noticeable sedation or motor impairment, as well as significant anxiolytic effects comparable to those of diazepam (p < 0.05). Good drug-likeness and CNS permeability were predicted for the lead compounds by ADME analysis. Conclusion: Both in silico and in vivo tests support the encouraging skeletal muscle relaxant and anxiolytic properties of the synthesized Schiff base hybrids. These results suggest their potential as top contenders for the development of innovative CNS-active medications.