In Vivo Screening and In Silico Structure-Based Characterization of Synthesized Oxadiazole Derivatives with Potential Anticonvulsant Activity

The main objective of this research was to evaluate the anticonvulsant activity of a series of newly synthesized oxadiazoles using spectroscopic, in vitro and in silico studies.

The in-vivo anticonvulsant activity of the synthesized oxadiazole derivatives was evaluated through maximal electroshock seizure (MES) and subcutaneous pentylenetetrazol (scPtz) tests in mice. Spectroscopic techniques were employed to characterize the synthesized compounds. Drug-likeness prediction and in silico ADME assessment, molecular docking, molecular dynamics simulation, and density functional theory calculation were performed to explore the potential of synthesized compounds.

The results of the in-vivo study revealed that compounds 6b, 6g, and 6h exhibited protection against PTZ-induced seizure in mice, indicating their potential as anticonvulsant agents. Drug-likeness prediction and In silico ADME assessment indicated that the synthesized compounds satisfied all the necessary requirements. Docking studies revealed that compound 6b exhibited the highest negative binding affinity against CaSRs, suggesting strong binding interactions. Stability of protein–ligand complex was confirmed using 100 ns molecular dynamics simulation. The calculated energies of frontier molecular orbitals using density functional theory indicated a good HOMO–LUMO gap for all the derivatives, further supporting their bioactivity.

The newly synthesized oxadiazoles, especially compounds 6b, 6g, and 6h, demonstrated promising anticonvulsant activity in the in-vivo tests. The molecular docking study revealed potential interactions with CaSRs, particularly for compound 6b. Molecular dynamics simulations confirmed the conformational stability of the docked protein–ligand complexes over 100 ns. Overall, this research provides valuable insights into the potential of synthesized oxadiazoles as anticonvulsant agents, paving the way for further drug development studies.