Anticonvulsant Activity of Halogen-Substituted Cinnamic Acid Derivatives and Their Effects on Glycosylation of PTZ-Induced Chronic Epilepsy in Mice

被引:6
作者
Cuan, Ye [1 ]
He, Xirui [1 ]
Zhao, Yuhui [1 ]
Yang, Jiajun [1 ]
Bai, Yajun [1 ,2 ]
Sun, Yin [1 ]
Zhang, Qiang [1 ]
Zhao, Zefeng [1 ]
Wei, Xiaoyang [1 ]
Zheng, Xiaohui [1 ]
机构
[1] Northwest Univ, Coll Life Sci, Key Lab Resource Biol & Biotechnol Western China, Minist Educ, 229 Taibai Rd, Xian 710069, Shaanxi, Peoples R China
[2] Northwest Univ, Coll Chem & Mat Sci, Key Lab Synthet & Nat Funct Mol Chem, Minist Educ, Xian 710127, Shaanxi, Peoples R China
来源
MOLECULES | 2018年 / 23卷 / 01期
关键词
epilepsy; cinnamic acid; anticonvulsant activities; glycosylation; neurotoxicity; ANTICANCER AGENTS;
D O I
10.3390/molecules23010076
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
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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页数:9
相关论文
共 23 条
[1]  
[Anonymous], 2014, EVID-BASED COMPL ALT, DOI DOI 10.1155/2014/642942
[2]   The relationship between pharmacokinetic parameters of carbamazepine and therapeutic response in epileptic patients [J].
Chbili, Chahra ;
Hassine, Anis ;
Laouani, Aicha ;
Ben Amor, Sana ;
Nouira, Manel ;
Ben Ammou, Sofiene ;
Saguem, Saad .
ARCHIVES OF MEDICAL SCIENCE, 2017, 13 (02) :353-360
[3]   3,4,5-Trimethoxycinnamic acid, one of the constituents of Polygalae Radix exerts anti-seizure effects by modulating GABAAergic systems in mice [J].
Chen, Chang-Yuan ;
Wei, Xu-Dong ;
Chen, Chang-Rui .
JOURNAL OF PHARMACOLOGICAL SCIENCES, 2016, 131 (01) :1-5
[4]  
Chitsaz A., 2013, INT J PREV MED, V4, P16
[5]   Cinnamic Acid Derivatives as Anticancer Agents-A Review [J].
De, P. ;
Baltas, M. ;
Bedos-Belval, F. .
CURRENT MEDICINAL CHEMISTRY, 2011, 18 (11) :1672-1703
[6]   ILAE Official Report: A practical clinical definition of epilepsy [J].
Fisher, Robert S. ;
Acevedo, Carlos ;
Arzimanoglou, Alexis ;
Bogacz, Alicia ;
Cross, J. Helen ;
Elger, Christian E. ;
Engel, Jerome, Jr. ;
Forsgren, Lars ;
French, Jacqueline A. ;
Glynn, Mike ;
Hesdorffer, Dale C. ;
Lee, B. I. ;
Mathern, Gary W. ;
Moshe, Solomon L. ;
Perucca, Emilio ;
Scheffer, Ingrid E. ;
Tomson, Torbjorn ;
Watanabe, Masako ;
Wiebe, Samuel .
EPILEPSIA, 2014, 55 (04) :475-482
[7]   Genes and epilepsy I: Epilepsy and genetic alterations [J].
Gitai, Daniel L. G. ;
Romcy-Pereira, Rodrigo N. ;
Gitai, Livia L. G. ;
Leite, Joao P. ;
Garcia-Cairasco, Norberto ;
Paco-Larson, Maria Luisa .
REVISTA DA ASSOCIACAO MEDICA BRASILEIRA, 2008, 54 (03) :272-278
[8]   Preliminary Evaluation of Anticonvulsant Activity of Some Aminoalkanol and Amino Acid Cinnamic Acid Derivatives [J].
Gunia, Agnieszka ;
Waszkielewicz, Anna M. ;
Cegla, Marek ;
Marona, Henryk .
LETTERS IN DRUG DESIGN & DISCOVERY, 2012, 9 (01) :37-43
[9]   The many roles for fluorine in medicinal chemistry [J].
Hagmann, William K. .
JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (15) :4359-4369
[10]   Anticonvulsant activities of α-asaronol ((E)-3′-hydroxyasarone), an active constituent derived from α-asarone [J].
He, Xirui ;
Bai, Yajun ;
Zeng, Min ;
Zhao, Zefeng ;
Zhang, Qiang ;
Xu, Ning ;
Qin, Fanggang ;
Wei, Xiaoyang ;
Zhao, Meimei ;
Wu, Ni ;
Li, Zehua ;
Zhang, Yajun ;
Fan, Tai-Ping ;
Zheng, Xiaohui .
PHARMACOLOGICAL REPORTS, 2018, 70 (01) :69-74