title: Anticonvulsant and Neurotoxicity of Some Novel 1-([1,3,4]thiadiazino[6,5- b]indol-3-yl Semicarbazides.
abstract: In the present study a series of new N(4)-(4-substituted benzylidene)-N(1)-([1,3,4]thiadiazino [6,5-b]indol-3-yl)semicarbazide (1-6), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-(1-(4-substituted phenyl)ethylidene)semicarbazide (7-10), N(4)-([1,3,4]thiadiazino[6,5-b]indol-3-yl)-N(1)-((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, (1)H and (13)C 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.
authors.affiliation: Department of Pharmaceutical Chemistry, Faculty of Pharmaceutical Sciences, SSTC, Bhilai-490020, Chhattisgarh, India. ravitasd@gmail.com.
authors.forename: Ravitas
authors.initials: R
authors.lastname: Deshmukh
authors.forename: Alok S
authors.initials: AS
authors.lastname: Thakur
authors.forename: Arvind K
authors.initials: AK
authors.lastname: Jha
authors.forename: Sudhir P
authors.initials: SP
authors.lastname: Kumar
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology*; D001522:Behavior, Animal / Q000187:drug effects; D004305:Dose-Response Relationship, Drug; D004597:Electroshock; D008297:Male; D051379:Mice; D020258:Neurotoxicity Syndromes / Q000523:psychology*; D010433:Pentylenetetrazole; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control; D012663:Semicarbazides / Q000138:chemical synthesis* / Q000494:pharmacology*; D013329:Structure-Activity Relationship
chemical_list: C000610193:4-((1,3,4)thiadiazino(6,5-b)indol-3-yl)-1-((4- hydroxyphenyl)(phenyl)methylene)semicarbazide; D000927:Anticonvulsants; D012663:Semicarbazides; D010433:Pentylenetetrazole