Title:Anticonvulsant and Neurotoxicity of Some Novel 1-([1,3,4]thiadiazino[6,5- b]indol-3-yl Semicarbazides
VOLUME: 16 ISSUE: 1
Author(s):Ravitas Deshmukh, Alok S. Thakur, Arvind K. Jha and Sudhir Kumar P.
Affiliation:Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, SSTC, Bhilai-490020, Chhattisgarh, India.
Keywords:Anticonvulsant activity, indole, maximal electroshock seizure test, neurotoxicity, semicarbazone.
Abstract:In the present study a series of new N4-(4-substituted benzylidene)-N1-([1,3,4]thiadiazino
[6,5-b]indol-3-yl)semicarbazide (1-6), N4-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N1-(1-(4—substituted
phenyl)ethylidene)semicarbazide (7-10), N4-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N1-((4-substituted
phenyl)(phenyl)methylene) semicarbazide. (11-14) have been synthesized from isatin and thiosemicarbazide
through multiple steps to meet structural necessities for the anticonvulsant activity. All the
newly prepared compounds were characterized by spectral techniques like FT-IR, 1H and 13C NMR,
EI-MS and elemental analysis. All the newly synthesized compounds were investigated for the anticonvulsant activity
against maximal electroshock induced seizures (MES) and subcutaneous pentylenetetrazole (scPTZ) models and their
neurotoxicity were also evaluated by rotarod test. The results obtained showed that 64% of the compounds showed protection
in the MES test and 36% of the compounds showed protection in ScPTZ test. Some of the compounds also showed
good activity after oral administration. Among the synthesized compounds, compound 14 was shown to be the most active
compound showing activity at 100 and 300 mg/kg in MES and ScPTZ test with prolonged duration of action. In the present
study, semicarbazones of hydroxy containing carbonyl compounds were depicted to be the potent molecule with low
neurotoxicity and prolong duration of action on oral administration. The result of the present study may be used for the future
development of novel anticonvulsants with broad spectrum of anticonvulsant activity.