2. Academic Validation
  3. Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents

Synthesis and Pharmacological Evaluation of Novel Benzenesulfonamide Derivatives as Potential Anticonvulsant Agents

  • Molecules. 2015 Sep 23;20(9):17585-600. doi: 10.3390/molecules200917585.
Zhiming Wang 1,  Jinping Li 2,  Xiao-Dong Zeng 3,  Xian-Ming Hu 4,  Xiaoju Zhou 5,  Xuechuan Hong 6
Affiliations

Affiliations

  • 1 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. zhiming.wang@whu.edu.cn.
  • 2 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. lijinping19891210@126.com.
  • 3 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. zxd201102@whu.edu.cn.
  • 4 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. xmhu@whu.edu.cn.
  • 5 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. xjzhou@whu.edu.cn.
  • 6 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. xhy78@whu.edu.cn.
PMID: 26404228 DOI: 10.3390/molecules200917585
Abstract

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.

Keywords

MES; anticonvulsant; scPTZ; sulfonamide.

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