SYNTHESIS AND PHARMACOLOGICAL EVALUATION OF SUBSTITUTED 1,3,4- THIADIAZOLE DERIVATIVES AS ANTICONVULSANT AGENTS

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Abstract

Epilepsy is considered as a brain disorder which involves repeated and spontaneous seizures. Seizures (convulsions) are defined as episodes of disturbed brain functions causing changes in attention or behavior. They are caused by abnormally excited electrical signals in the brain. Comprehensive literature assessment revealed that amongst the compounds studied for anticonvulsant activity; 1,3,4-thiadiazole nucleus showed potent anticonvulsant activity. Acetazolamide and methazolamide are the examples of 2,5-disubstituted-1,3,4- thiadiazole analogues. Hydrazine hydrate and isothiocyanate are used for formation of intermediate and reacted further with substituted aromatic aldehydes in the presence of thiourea to give final derivatives, substituted 1,3,4-thiadiazole. This title compound in step-1 was prepared by stirring of hydrazine hydrate with isothiocyanate whereas in step-2, substituted benzaldehyde was used in presence of thiourea. All synthesized compounds were characterized by physical and spectral characteristics. Structure elucidation of the synthesized compounds was carried out by spectral analysis, FTIR and Mass analysis. PTZ model was used to determine anticonvulsant activity of the final synthesized compounds using Carbamazepine as a standard drug. All synthesized compounds of showed no sedation side effect as compared to reference standard (carbamazepine). The present study indicated that 4-fluoro substituted compound (6b) showed significant protection against pentylenetetrazole induced convulsions as well as mortality within 24 h in mice. It also decreased number of convulsions (P<0.01) and increased onset time for clonic convulsion (P<0.05) which was statistically significant in comparison to control. Study could further be investigated to design & identify lead compound.