Anticonvulsant Activity of Halogen-Substituted Cinnamic Acid Derivatives and Their Effects on Glycosylation of PTZ-Induced Chronic Epilepsy in Mice.
Anticonvulsant Activity of Halogen-Substituted Cinnamic Acid Derivatives and Their Effects on Glycosylation of PTZ-Induced Chronic Epilepsy in Mice.
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DOI：
10.3390/molecules23010076
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发表时间：
2017-12-29
期刊：
影响因子：
--
通讯作者：
Zheng X
中科院分区：
文献类型：
--
作者：
Cuan Y;He X;Zhao Y;Yang J;Bai Y;Sun Y;Zhang Q;Zhao Z;Wei X;Zheng X
癫痫是一种常见的慢性神经系统疾病，迫切需要开发新的抗癫痫药物。本研究采用最大电休克发作（MES）和旋转棒试验（Tox）对12种肉桂酸氟、氯、溴和三氟甲基取代衍生物进行了抗惊厥活性和神经毒性的筛选。三个测试的化合物（化合物3，6和12）显示出较好的抗惊厥作用和较低的神经毒性。中位有效剂量（ED_（50））分别为47.36、75.72和70.65 mg/kg，中位毒性剂量（TD_（50））均大于500 mg/kg，具有较好的保护作用。同时，它们在小鼠中显示戊四唑（PTZ）ED 50值分别为245.2、>300和285.2 mg/kg。特别是，最具活性的化合物3显示出突出的抗惊厥作用，并且具有较低的毒性。因此，本研究拟利用糖组学技术进一步探讨3对慢性癫痫小鼠糖基化改变的抗癫痫作用机制。凝集素基因芯片结果显示癫痫与糖基化异常密切相关，3可以逆转scPTZ诱导的小鼠癫痫中糖基化异常。本研究为今后发现基于糖蛋白在癫痫中的精确改变的潜在生物标志物以评价抗癫痫药物提供了新的思路。
Epilepsy is a common chronic neurological disorder disease, and there is an urgent need for the development of novel anticonvulsant drugs. In this study, the anticonvulsant activities and neurotoxicity of 12 cinnamic acid derivatives substituted by fluorine, chlorine, bromine, and trifluoromethyl groups were screened by the maximal electroshock seizure (MES) and rotarod tests (Tox). Three of the tested compounds (compounds 3, 6 and 12) showed better anticonvulsant effects and lower neurotoxicity. They showed respective median effective dose (ED50) of 47.36, 75.72 and 70.65 mg/kg, and median toxic dose (TD50) of them was greater than 500 mg/kg, providing better protective indices. Meanwhile, they showed a pentylenetetrazol (PTZ) ED50 value of 245.2, >300 and 285.2 mg/kg in mice, respectively. Especially, the most active compound 3 displayed a prominent anticonvulsant profile and had lower toxicity. Therefore, the antiepileptic mechanism of 3 on glycosylation changes in chronic epilepsy in mice was further investigated by using glycomics techniques. Lectin microarrays results showed that epilepsy was closely related to abnormal glycosylation, and 3 could reverse the abnormal glycosylation in scPTZ-induced epilepsy in mice. This work can provide new ideas for future discovery of potential biomarkers for evaluation of antiepileptic drugs based on the precise alterations of glycopatterns in epilepsy.
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DOI：
10.1590/s0104-42302008000300023
发表时间：
2008-06-01
期刊：
Revista da Associação Médica Brasileira
影响因子：
--
作者：
Gitaí, Daniel L. G.;Romcy-Pereira, Rodrigo N.;Paço-Larson, Maria Luisa
通讯作者：
Paço-Larson, Maria Luisa
影响因子：
3.7
作者：
Masic, Anita;Hernandez, Ana Maria Valencia;Schurigt, Uta
通讯作者：
Schurigt, Uta
影响因子：
5.6
作者：
Fisher, Robert S.;Acevedo, Carlos;Wiebe, Samuel
通讯作者：
Wiebe, Samuel
影响因子：
3.4
作者：
Zhu B;Shang B;Li Y;Zhen Y
通讯作者：
Zhen Y
影响因子：
3.5
作者：
Chen, Chang-Yuan;Wei, Xu-Dong;Chen, Chang-Rui
通讯作者：
Chen, Chang-Rui