Effect of sulfonamide derivatives of phenylglycine on scopolamine‐induced amnesia in rats

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.

The selective butyrylcholinesterase inhibitor UW‐MD‐95 shows symptomatic and neuroprotective effects in a pharmacological mouse model of Alzheimer's disease

“…Second, S06‐1011 and S06‐1031, two compounds containing a 3‐(benzimidazol‐2‐yl)‐1,2,5‐oxadiazole core, and showing a selective and sub‐micromolar inhibitory potency on BChE, attenuated scopolamine and Aβ 1‐42 ‐induced memory deficits in the Morris water maze in mice 50 . Third, sulfonamide derivatives of phenylglycine attenuated, after a 7‐day daily treatment before scopolamine, the memory deficits of rats in the Y‐maze and Barnes tests 51 . The physiological mode of action is likely related to facilitation of the cholinergic systems for both the scopolamine and Aβ amnesia.…”

“… 50 Third, sulfonamide derivatives of phenylglycine attenuated, after a 7‐day daily treatment before scopolamine, the memory deficits of rats in the Y‐maze and Barnes tests. 51 The physiological mode of action is likely related to facilitation of the cholinergic systems for both the scopolamine and Aβ amnesia. Indeed, UW‐MD‐95 shared the ability to prevent scopolamine‐ and Aβ 25‐35 ‐induced learning deficits in mice, thereby confirming a direct and rapid involvement of BChE activity in memory processes.…”