Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation

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• 作者：Jin-Wu Yan ; Yan-Ping Li ; Wen-Jie Ye ; Shuo-Bin Chen ; Jin-Qiang Hou ; Jia-Heng Tan ; ^{tanjiah@mail.sysu.edu.cn} ; Tian-Miao Ou ; Ding Li ; Lian-Quan Gu ; Zhi-Shu Huang ; ^{ceshzs@mail.sysu.edu.cn}
• 关键词：Isaindigotone derivatives ; AChE inhibition ; A尾 aggregation inhibition ; Anti-Alzheimer agents
• 刊名：Bioorganic and Medicinal Chemistry
• 出版年：2012
• 期刊代码：9_09680896
• 类别：ch
• 出版时间：15 April, 2012
• 卷：20
• 期：8
• 页码：2527-2534
• 文件大小：1162 K

摘要

A series of isaindigotone derivatives and analogues were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced 尾-amyloid (A尾) aggregation. The synthetic compounds had IC₅₀ values at micro or nano molar range for cholinesterase inhibition, and some compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE, which were much better than the isaindigotone derivatives previously reported by our group. Most of these compounds showed higher self-induced A尾 aggregation inhibitory activity than a reference compound curcumin. The structure-activity relationship studies revealed that the derivatives with higher inhibition activity on AChE also showed higher selectivity for AChE over BuChE. Compound 6c exhibiting excellent inhibition for both AChE and self-induced A尾 aggregation was further studied using CD, EM, molecular docking and kinetics.