Synthesis and Biological Evalution of 1,3,4-Thiadiazole Derivatives as Anti-Convulsant Agents

Abstract

Epilepsy is a brain disorder involving repeated, spontaneous seizures of any type. Seizures (convulsions) are episodes of disturbed brain function that cause changes in attention or behaviour. They are caused by abnormally excited electrical signals in the brain. Extensive literature review revealed that amongst the compounds studied for anticonvulsant activity; 1,3,4-thiadiazole nucleus ring showed potent anticonvulsant activity. Acetazolamide and methazolamide are the examples of 2,5-disubstituted-1,3,4- thiadiazole analogues. Hydrazine hydrate and phenylisothiocyanate are used for formation of intermediate and further reacted with substituted benzaldehyde in the presence of thiourea to finally synthesized 1,3,4-thiadiazole were designed and synthesized. This title compound in step-1 was prepared by stirring of hydrazine hydrate with phenylisothiocyanate whereas in 2nd step, substituted benzaldehyde was used in presence of thiourea. Structure elucidation of the synthesized compounds was done by spectral analysis such as IR, MASS. The anticonvulsant activity of the title compounds was evaluated by using PTZ model (60mg/kg) and Carbamazepine taking as a reference standard (100 mg/kg). All synthesized compounds of showed no sedation side effect as compared to reference standard (carbamazepine). The present study indicated that 4-fluoro substituted compounds (KK-2) 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 increase 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.