Synthesis and anticonvulsant activity of N-(2-hydroxyethyl) cinnamamide derivatives.
A series of novel N-(2-hydroxyethyl) cinnamamide derivatives were synthesized and screened for their anticonvulsant activities by the maximal electroshock (MES) test and their neurotoxicity was evaluated by the rotarod neurotoxicity test (Tox). The MES test showed that compounds I(N-(2-hydroxyethyl) cinnamamide) and 1d ((E)-3-(3-fluorophenyl)-N-(2-hydroxyethyl)acrylamide) were found to possess better anticonvulsant activity but also had lower toxicity. In the anti-MES potency test, these compounds exhibited median effective dose (ED(50)) of 17.7 and 17.0 mg/kg, respectively, and median toxicity dose (TD(50)) of 154.9 and 211.1, respectively, resulting in a protective index (PI) of 8.8 and 12.4, respectively, which is much greater than the PI of the marked antiepileptic drug carbamazepine. To further investigate the effects of the anticonvulsant activity in several different models, compounds I and 1d were tested against convulsions induced by chemical substances, including pentylenetetrazole (PTZ), isoniazid, 3-mercaptopropionic acid, and thiosemicarbazide.
Guan
Li-Ping
LP
Key Laboratory of Organism Functional Factors of the Changbai Mountain (Yanbian University), Ministry of Education, Yanji, Jilin 133002, PR China.
Wei
Cheng-Xi
CX
Deng
Xian-Qing
XQ
Sui
Xin
X
Piao
Hu-Ri
HR
Quan
Zhe-Shan
ZS
D015097:3-Mercaptopropionic Acid; D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use* / Q000633:toxicity; D002934:Cinnamates / Q000138:chemical synthesis / Q000737:chemistry* / Q000627:therapeutic use* / Q000633:toxicity; D004597:Electroshock; D007538:Isoniazid; D051379:Mice; D010433:Pentylenetetrazole; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy*; D012663:Semicarbazides; D013329:Structure-Activity Relationship
D000927:Anticonvulsants; D002934:Cinnamates; D012663:Semicarbazides; C005151:thiosemicarbazide; D015097:3-Mercaptopropionic Acid; D007538:Isoniazid; D010433:Pentylenetetrazole; C411088:cinnamamide