Synthesis and Anticonvulsant Effect of Novel Thiazolidinedione Containing Benzene-sulfonylurea and Sulfonylthiourea Derivatives

A newer series of 1-(4-substitutedphenyl)-3-(4-((2,4-dioxothiazolidin-5-lidene)methyl)phenyl sulfonyl)urea/thiourea (4a-l) were synthesized for their anticonvulsant activity. The activity is attributed to its potential to restrain astrocytic Na+, 2HCl, and K+ co-transport similar to torasemide which has sulfonylurea in its structure. Torasemide having the similar action as the furosemide that obstructs kainic acid-induced electrical discharges observed from cortex and it has neuroprotective agents, for instance antagonizing the N-methyl-D-aspartate (NMDA) and non-NMDA receptors for evaluating antiepileptic activity. The structures of new derivatives were established by elemental analysis and spectroscopic techniques viz. FTIR, 1H NMR and LC-MS. The all twelve derivatives were assessed for anticonvulsant activity at three different doses at 30, 100 and 300 mg/kg body weight into maximal electroshock (MES) and subcutaneous pentylenetetrazole (sports) models. Compounds 4c and 4e were formed to be most active among all the derivatives for both the models of anticonvulsant activity. Beside these compounds 4g, 4i and 4k also possessed the prominent anticonvulsant activity devoid of any neurotoxicity. The sulfonylurea and sulfonylthiourea both were proved to be effective anticonvulsant pharmacophore. Other structure activity relationships were established by considering the aspect of substitution in the lead.