Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo 11562, Egypt.
Biochemistry Department, Cairo General Hospital, Egypt.
Bioorg Chem. 2018 Feb;76:210-217. doi: 10.1016/j.bioorg.2017.11.008. Epub 2017 Nov 15.
A new series of oxopyrrolidines was synthesized and evaluated for their effect on Alzheimer's disease by measuring their inhibitory activity against acetyl cholinesterase enzyme and amyloid β 42 protein. Most of the compounds showed good inhibitory activity with ethyl 2-(2-(2, 6-dimethylphenylcarbamoyl)- 5-oxopyrrolidin-1-yl) acetate (V) having the highest activity against acetyl cholinesterase with IC value 1.84 ng/g tissue compared to standard donepezil 3.34 ng/g tissue. Furthermore, compound 1-((4-(4-chlorophenyl) piperazin-1-yl) methyl)-N-(2,6-dimethylphenyl)-5- oxopyrrolidine- 2-carboxamide (IIIe) displayed the highest activity against β 42 protein with IC value of 11.3 Pg/g tissue compared to 18.4 Pg/g tissue of donepezil.
合成了一系列新的氧代吡咯烷，并通过测量它们对乙酰胆碱酯酶和淀粉样蛋白β 42 蛋白的抑制活性来评估它们对阿尔茨海默病的作用。大多数化合物表现出良好的抑制活性，其中乙基 2-(2-(2,6-二甲基苯甲酰胺基)-5-氧代吡咯烷-1-基)乙酸酯(V)对乙酰胆碱酯酶的抑制活性最高，IC 值为 1.84 ng/g 组织，而标准药物多奈哌齐为 3.34 ng/g 组织。此外，化合物 1-((4-(4-氯苯基)哌嗪-1-基)甲基)-N-(2,6-二甲基苯基)-5-氧代吡咯烷-2-甲酰胺(IIIe)对β 42 蛋白的抑制活性最高，IC 值为 11.3 Pg/g 组织，而多奈哌齐为 18.4 Pg/g 组织。
