title: Synthesis and screening of substituted thiosemicarbazone derivatives: an approach towards novel anticonvulsant search.
abstract: A series of thiosemicarbazones of halogen substituted benzaldehydes, benzophenone and acetophenone were synthesized using an appropriate synthetic route and characterized by thin layer chromatography and spectral analysis. The anticonvulsant activity of synthesized compounds was established in three seizures models which includes maximal electroshock (MES), subcutaneous pentylene tetrazole (scPTZ) induced seizures and minimal neurotoxicity test. Five compounds out of 21 exhibited protection in MES test while only one compound showed protection in scPTZ screen. Two compounds were found to be active in minimal clonic seizure (6Hz) model. Compound PS6 i.e. 2-(3-bromobenzylidene)-N-(4-chlorophenyl) hydrazinecarbothioamide emerged as the most active compound with MES ED50 of more than 50mg/kg and pI greater than 12, which is found to be better than the prototype drug, Phenytoin. The compound has shown neuroprotection in kainic acid model with IC50 value of 40.97 µM. It has also shown mild activation effect on CYP 269 and CYP 2C9 enzymes, indicating the usefulness of thiosemicarbazones as anticonvulsants.
authors.affiliation: Kalka Institute for Research and Advanced Studies, Partapur Bypass, Meerut, Uttar Pradesh, India.
authors.forename: Priyanka
authors.initials: P
authors.lastname: Singh
authors.forename: Jainendra
authors.initials: J
authors.lastname: Jain
authors.forename: Reema
authors.initials: R
authors.lastname: Sinha
authors.forename: Abdul
authors.initials: A
authors.lastname: Samad
authors.forename: Rajeev
authors.initials: R
authors.lastname: Kumar
authors.forename: Manav
authors.initials: M
authors.lastname: Malhotra
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use; D003292:Convulsants / Q000009:adverse effects; D004597:Electroshock; D006801:Humans; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000009:adverse effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D017208:Rats, Wistar; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy / Q000517:prevention & control; D013882:Thiosemicarbazones / Q000138:chemical synthesis* / Q000737:chemistry* / Q000627:therapeutic use
chemical_list: D000927:Anticonvulsants; D003292:Convulsants; D013882:Thiosemicarbazones; D010433:Pentylenetetrazole