title: Design and Synthesis of 5-Substituted Benzo[d][1,3]dioxole Derivatives as Potent Anticonvulsant Agents.
abstract: A series of 5-substituted benzo[d][1,3]dioxole derivatives was designed, synthesized, and tested for anticonvulsant activity using the maximal electroshock (MES) and subcutaneous pentylenetetrazole (scPTZ) screens. Neurotoxicity was determined by rotarod test. In the preliminary screening, six compounds, 3a, 3c, 3d, and 4d-f, showed promising anticonvulsant activities in the MES model, and compounds 4c and 4d exhibited full protection against seizures at doses of 300 mg/kg in the scPTZ model. Among the synthesized compounds, 3c as the most active compound showed high protection against the MES-induced seizures with an ED50value of 9.8 mg/kg and a TD50value of 229.4 mg/kg after intraperitoneal injection into mice, thus providing compound 3c with a high protective index (TD50/ED50) of 23.4 comparable to those of reference antiepileptic drugs.
authors.affiliation: College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, China.|College of Pharmacy, Hubei University of Science and Technology, Xianning, China.
authors.forename: Shiyang
authors.initials: S
authors.lastname: Dong
authors.affiliation: College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, China.|The National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, China.
authors.forename: Tiantian
authors.initials: T
authors.lastname: Wang
authors.affiliation: College of Pharmacy, Hubei University of Science and Technology, Xianning, China.
authors.forename: Chundi
authors.initials: C
authors.lastname: Hu
authors.affiliation: College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Xiaodong
authors.initials: X
authors.lastname: Chen
authors.affiliation: College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, China.|The National Pharmaceutical Engineering Center for Solid Preparation in Chinese Herbal Medicine, Nanchang, China.
authors.forename: Yi
authors.initials: Y
authors.lastname: Jin
authors.affiliation: College of Pharmacy, JiangXi University of Traditional Chinese Medicine, Nanchang, China.
authors.forename: Zengtao
authors.initials: Z
authors.lastname: Wang
mesh_terms: D000818:Animals; D000927:Anticonvulsants / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology*; D004149:Dioxoles / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D004305:Dose-Response Relationship, Drug; D015195:Drug Design; D004597:Electroshock; D051379:Mice; D010433:Pentylenetetrazole; D045442:Rotarod Performance Test; D012640:Seizures / Q000139:chemically induced / Q000517:prevention & control*; D013329:Structure-Activity Relationship
chemical_list: D000927:Anticonvulsants; D004149:Dioxoles; D010433:Pentylenetetrazole
keywords: Anticonvulsant activity; Benzo[d][1,3]dioxole derivatives; Design; Synthesis