新型1,3二氧杂环戊烯并4,5-f异吲哚酮衍生物的设计、合成与活性研究

Design, synthesis and biological evaluation of novel 1,3dioxolo4,5-fisoindolone derivatives

摘要: 本文设计、合成了一系列新型1,3二氧杂环戊烯并4,5-f异吲哚酮衍生物, 并对其进行了乙酰胆碱酯酶抑制活性以及由东莨菪碱致小鼠记忆障碍的改善作用测试。实验结果表明目标化合物对乙酰胆碱酯酶(AChE)均有抑制作用, IC₅₀值在微摩尔级, 其中化合物I₁(IC₅₀=0.086 µmol·L^-1)和I₂(IC₅₀=0.080 µmol·L^-1)对AChE的抑制活性较好, 与阳性药多奈哌齐(IC₅₀=0.094 µmol·L^-1)相当; 且化合物I₁～I₄均具有改善由东莨菪碱引起的小鼠记忆障碍的作用。

Abstract: A series of 1,3dioxolo4,5-fisoindolone derivatives were designed, synthesized and evaluated as inhibitors of acetylcholinesterases (AChE). Furthermore, their effects on memory impairment of mice induced by scopolamine were investigated with step-through test. The results suggested that most of the target compounds exhibited potential inhibition on AChE with IC₅₀ values at micromolar range. Compounds I₁ (IC₅₀ value of 0.086 �mol·L^-1) and I₂ (IC₅₀ value of 0.080 �mol·L^-1) showed the strongest AChE inhibitory activity, which are equipotent to donepezil (IC₅₀ value of 0.094 �mol·L^-1). Moreover, compounds I₁-I₄ could improve the memory impairment induced by scopolamine in mice.