Synthesis and Evaluation of the Anticonvulsant Activities of 4-(2-(Alkylthio)benzo[d]oxazol-5-yl)-2,4-dihydro-3H-1,2,4-triazol-3-ones

In this study, a novel series of 4-(2-(alkylthio)benzo[ ]oxazol-5-yl)-2,4-dihydro-3 -1,2,4-triazol-3-ones ( - ) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) se...

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Bibliographic Details
Published in:Molecules (Basel, Switzerland) Switzerland), 2018-03, Vol.23 (4), p.756
Main Authors: Song, Ming-Xia, Wang, Zhen-Yuan, He, Shi-Hui, Yu, Sheng-Wang, Chen, Shi-Long, Guo, Dong-Fu, Zhao, Wen-Hao, Deng, Xian-Qing
Format: Article
Language:English
Subjects:
Animal models
anticonvulsant
Anticonvulsants
benzoxazole
Brain
Carbamazepine
Enzyme-linked immunosorbent assay
maximal electroshock
Neurotoxicity
Pentylenetetrazole
Pretreatment
Seizing
Seizures
triazolone
Valproic acid
γ-Aminobutyric acid
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Summary:In this study, a novel series of 4-(2-(alkylthio)benzo[ ]oxazol-5-yl)-2,4-dihydro-3 -1,2,4-triazol-3-ones ( - ) was designed and synthesized. The anticonvulsant activities of these compounds were evaluated by using the maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) seizure models in mice. The neurotoxicity of these compounds was evaluated using the rotarod neurotoxicity test. The majority of compounds showed anti-MES activities at 100 or 300 mg/kg. Compound was considered to be the most promising, based on its potency against MES- and PTZ-induced seizures with ED values of 23.7 and 18.9 mg/kg, respectively. The TD value of was 284.0 mg/kg, which resulted in a higher protective index (PI = TD /ED ) value than that of carbamazepine and valproate. In an ELISA test, compound significantly increased the γ-aminobutyric acid (GABA) content in mouse brain. In addition, pretreatment with thiosemicarbazide (an inhibitor of the GABA synthesizing enzyme) significantly decreased the activity of in the MES model, which suggests that the mechanism through which compound elicits its anticonvulsive action is at least in part through increasing the GABA level in the brain.
ISSN:1420-3049
1420-3049
DOI:10.3390/molecules23040756