Effect of sulfonamide derivatives of phenylglycine on scopolamine‐induced amnesia in rats
Ankit Ganeshpurkar,
Ravi Singh,
Pratigya Tripathi,
Qadir Alam,
Sairam Krishnamurthy,
Ashok Kumar,
Sushil K. Singh
Affiliations
Ankit Ganeshpurkar
Department of Pharmaceutical Engineering and Technology, Pharmaceutical Chemistry Research Laboratory I Indian Institute of Technology (Banaras Hindu University) Varanasi India
Ravi Singh
Department of Pharmaceutical Engineering and Technology, Pharmaceutical Chemistry Research Laboratory I Indian Institute of Technology (Banaras Hindu University) Varanasi India
Pratigya Tripathi
Department of Pharmaceutical Engineering and Technology, Neurotherapeutics Laboratory Indian Institute of Technology (Banaras Hindu University) Varanasi Uttar Pradesh India
Qadir Alam
Department of Pharmaceutical Engineering and Technology, Neurotherapeutics Laboratory Indian Institute of Technology (Banaras Hindu University) Varanasi Uttar Pradesh India
Sairam Krishnamurthy
Department of Pharmaceutical Engineering and Technology, Neurotherapeutics Laboratory Indian Institute of Technology (Banaras Hindu University) Varanasi Uttar Pradesh India
Ashok Kumar
Department of Pharmaceutical Engineering and Technology, Pharmaceutical Chemistry Research Laboratory I Indian Institute of Technology (Banaras Hindu University) Varanasi India
Sushil K. Singh
Department of Pharmaceutical Engineering and Technology, Pharmaceutical Chemistry Research Laboratory I Indian Institute of Technology (Banaras Hindu University) Varanasi India
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.
