Effect of sulfonamide derivatives of phenylglycine on scopolamine-induced amnesia in rats.
Ankit GaneshpurkarRavi SinghPratigya TripathiQadir AlamSairam KrishnamurthyAshok KumarSushil Kumar SinghPublished in: Ibrain (2023)
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.
Keyphrases
- molecular dynamics
- prefrontal cortex
- oxidative stress
- density functional theory
- diabetic rats
- high glucose
- cognitive impairment
- blood brain barrier
- molecular dynamics simulations
- drug induced
- small molecule
- nitric oxide
- endothelial cells
- sleep quality
- combination therapy
- binding protein
- brain injury
- replacement therapy
- smoking cessation