title: Synthesis and Biological Evaluation of Novel Benzothiazole Derivatives as Potential Anticonvulsant Agents.
abstract: New benztriazoles with a mercapto-triazole and other heterocycle substituents were synthesized and evaluated for their anticonvulsant activity and neurotoxicity by using the maximal electroshock (MES), subcutaneous pentylenetetrazole (scPTZ), and rotarod neurotoxicity (TOX) tests. Among the compounds studied, compound 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((3-fluorobenzyl) oxy)benzo[d]thiazol-2-yl)acetamide (5i) and 2-((1H-1,2,4-triazol-3-yl)thio)-N-(6-((4-fluorobenzyl)oxy) benzo[d] thiazol-2-yl)acetmide (5j) were the most potent, with an ED50 value of 50.8 mg/kg and 54.8 mg/kg in the MES test and 76.0 mg/kg and 52.8 mg/kg in the scPTZ seizures test, respectively. They also showed lower neurotoxicity and, therefore a higher protective index. In particular, compound 5j showed high protective index (PI) values of 8.96 in the MES test and 9.30 in the scPTZ test, which were better than those of the standard drugs used as positive controls in this study.
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. 2013001048@ybu.edu.cn.
authors.forename: Da-Chuan
authors.initials: DC
authors.lastname: Liu
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. zhjzhishixiang@163.com.
authors.forename: Hong-Jian
authors.initials: HJ
authors.lastname: Zhang
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. cmjin@ybu.edu.cn.
authors.forename: Chun-Mei
authors.initials: CM
authors.lastname: Jin
authors.affiliation: Key Laboratory of Natural Resources and Functional Molecules of the Changbai Mountain, Affiliated Ministry of Education, College of Pharmacy, Yanbian University, Yanji 133002, China. zsquan@ybu.edu.cn.
authors.forename: Zhe-Shan
authors.initials: ZS
authors.lastname: Quan
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000494:pharmacology; D052160:Benzothiazoles / Q000138:chemical synthesis* / Q000494:pharmacology; D003292:Convulsants / Q000008:administration & dosage; D004195:Disease Models, Animal; D015195:Drug Design; D004597:Electroshock; D006801:Humans; D007274:Injections, Intraperitoneal; D051379:Mice; D015394:Molecular Structure; D010433:Pentylenetetrazole / Q000008:administration & dosage; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced / Q000188:drug therapy* / Q000503:physiopathology; D013329:Structure-Activity Relationship; D023382:Toxicity Tests, Acute
chemical_list: D000927:Anticonvulsants; D052160:Benzothiazoles; D003292:Convulsants; D010433:Pentylenetetrazole
keywords: anticonvulsant; benzothiazole; maximal electroshock; mercapto-triazole; neurotoxicity; pentylenetetrazole; synthesis