Background: Benzothiazole is an organosulfur heterocyclic compound that has a considerable
place in drug discovery due to significant pharmacological actions.
Objective: The main objective of the present study was to synthesize some novel 2-(5-substituted
1,3,4-oxadiazole-2-yl)-1,3-benzothiazole derivatives and evaluate them for their anticonvulsant
activity using in silico and in vivo methods.
Methods: A set of sixteen 2-(5-substituted 1, 3, 4-oxadiazole-2-yl)-1, 3-benzothiazole derivatives
were prepared using multi-step reactions starting from o-amino-thiophenol and characterized by
suitable spectral techniques. The synthesized compounds were evaluated for anticonvulsant activity
using in silico and in vivo methods. In silico molecular docking study was performed using
Molegro Virtual Docker software to analyze binding modes of compounds with the internal ligand
of PDB ID: 1OHY and 1OHV; and in vivo pharmacological activities were tested for both
generalized tonic-clonic seizures and generalized absence (petit mal) seizures using Maximal
Electrical Shock and PTZ-induced seizure models, respectively.
Results: Some new 2-(5-substituted-1,3,4-oxadiazole-2-yl)-1,3- benzothiazole (5a-5p) were successfully
synthesized by finally refluxing 1, 3-benzothiazole-2-carboxyhydrazide with different
aromatic acids in phosphoryl chloride. Docking results showed that compounds 5c, 5j, and 5m
were found to have the highest number of H-bond interactions; i.e. 4, 4, and 7 respectively with
target proteins 1OHY and 6, 3, and 4 respectively with target protein 1OHV, whereas phenytoin
showed only two H-bonding with both proteins. In the Maximal electroshock seizure method, the
synthesized compounds 5h, 5k and 5o demonstrated potent anticonvulsant activity against the
tonic seizure with a significant decrease in tonic hind leg extension period with a mean duration
of 7.9, 7.4, and 7.0 sec respectively, as compared to the other synthesized compounds. In contrast,
in the PTZ-induced seizure model, compounds 5c, 5h, and 5m showed protection against
clonic convulsion with significant elevation in the onset time of clonic convulsion at 311.2,
308.0, and 333.11 sec, respectively.
Conclusion: Thus, from the results, it can be concluded that compound 5h, a benzothiazole derivative
endowed with an oxadiazole ring, can be developed as a potential anticonvulsant agent.