Ankit Ganeshpurkar, Ravi Singh, Pratigya Tripathi, Qadir Alam, Sairam Krishnamurthy, Ashok Kumar, Sushil K. Singh
{"title":"Effect of sulfonamide derivatives of phenylglycine on scopolamine-induced amnesia in rats","authors":"Ankit Ganeshpurkar, Ravi Singh, Pratigya Tripathi, Qadir Alam, Sairam Krishnamurthy, Ashok Kumar, Sushil K. Singh","doi":"10.1002/ibra.12092","DOIUrl":null,"url":null,"abstract":"<p>Alzheimer's disease is a neurodegenerative disease responsible for dementia and other neuropsychiatric symptoms. In the present study, compounds <b>30</b> and <b>33</b>, developed earlier in our laboratory as selective butyrylcholinesterase inhibitors, were tested against scopolamine-induced amnesia to evaluate their pharmacodynamic effect. The efficacy of the compounds was determined by behavioral experiments using the Y-maze and the Barnes maze and neurochemical testing. Both compounds reduced the effect of scopolamine treatment in the behavioral tasks at a dose of 20 mg/kg. The results of the neurochemical experiment indicated a reduction in cholinesterase activity in the prefrontal cortex and the hippocampus. The levels of antioxidant enzymes superoxide dismutase and catalase were restored compared to the scopolamine-treated groups. The docking study on rat butyrylcholinesterase (BChE) indicated tight binding, with free energies of −9.66 and −10.23 kcal/mol for compounds <b>30</b> and <b>33</b>, respectively. The two aromatic amide derivatives of <i>2-phenyl-2-(phenylsulfonamido) acetic acid</i> produced stable complexes with rat BChE in the molecular dynamics investigation.</p>","PeriodicalId":94030,"journal":{"name":"Ibrain","volume":null,"pages":null},"PeriodicalIF":0.0000,"publicationDate":"2023-02-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"https://onlinelibrary.wiley.com/doi/epdf/10.1002/ibra.12092","citationCount":"0","resultStr":null,"platform":"Semanticscholar","paperid":null,"PeriodicalName":"Ibrain","FirstCategoryId":"1085","ListUrlMain":"https://onlinelibrary.wiley.com/doi/10.1002/ibra.12092","RegionNum":0,"RegionCategory":null,"ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"","JCRName":"","Score":null,"Total":0}
引用次数: 0
Abstract
Alzheimer's disease is a neurodegenerative disease responsible for dementia and other neuropsychiatric symptoms. In the present study, compounds 30 and 33, developed earlier in our laboratory as selective butyrylcholinesterase inhibitors, were tested against scopolamine-induced amnesia to evaluate their pharmacodynamic effect. The efficacy of the compounds was determined by behavioral experiments using the Y-maze and the Barnes maze and neurochemical testing. Both compounds reduced the effect of scopolamine treatment in the behavioral tasks at a dose of 20 mg/kg. The results of the neurochemical experiment indicated a reduction in cholinesterase activity in the prefrontal cortex and the hippocampus. The levels of antioxidant enzymes superoxide dismutase and catalase were restored compared to the scopolamine-treated groups. The docking study on rat butyrylcholinesterase (BChE) indicated tight binding, with free energies of −9.66 and −10.23 kcal/mol for compounds 30 and 33, respectively. The two aromatic amide derivatives of 2-phenyl-2-(phenylsulfonamido) acetic acid produced stable complexes with rat BChE in the molecular dynamics investigation.