Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents
Zhiming Wang,
Jinping Li,
Xiao-Dong Zeng,
Xian-Ming Hu,
Xiaoju Zhou,
Xuechuan Hong
Affiliations
Zhiming Wang
These authors contributed equally to this work.
Jinping Li
These authors contributed equally to this work.
Xiao-Dong Zeng
State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan 430071, China
Xian-Ming Hu
State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan 430071, China
Xiaoju Zhou
State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan 430071, China
Xuechuan Hong
State Key Laboratory of Virology, Key Laboratory of Combinatorial Biosynthesis and Drug Discovery, Ministry of Education, Wuhan University School of Pharmaceutical Sciences, 185 Donghu Road, Wuhan 430071, China
A novel series of benzenesulfonamide derivatives containing 4-aminobenzenesul-fonamide and α-amides branched valproic acid or 2,2-dimethylcyclopropanecarboxylic acid moieties were synthesized and screened for their anticonvulsant activities in mice maximal electroshock seizure (MES) and subcutaneous pentylenetetrazole (scPTZ) test. The activity experimental study showed that 2,2-dipropyl-N1-(4-sulfamoylphenyl)malonamide (18b) had the lowest median effective dose (ED50) of 16.36 mg/kg in MES test, and 2,2-dimethyl-N-(4-sulfamoylphenyl)cyclopropane-1,1-dicarboxamide (12c) had the lowest ED50 of 22.50 mg/kg in scPTZ test, which resulted in the protective indexe (PI) of 24.8 and 20.4, respectively. These promising data suggest the new compounds have good potential as new class of anticonvulsant agents with high effectiveness and low toxicity for the treatment of epilepsy.
