Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation.
Design, synthesis and evaluation of isaindigotone derivatives as dual inhibitors for acetylcholinesterase and amyloid beta aggregation.
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DOI：
10.1016/j.bmc.2012.02.061
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发表时间：
2012-04
影响因子：
3.5
通讯作者：
Jin-wu Yan;Yan-ping Li;Wen-Jie Ye;Shuo-Bin Chen;Jin-Qiang Hou;Jia-Heng Tan;Tian-Miao Ou;Ding Li;L. Gu;Zhishu Huang
中科院分区：
文献类型：
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作者：
Jin-wu Yan;Yan-ping Li;Wen-Jie Ye;Shuo-Bin Chen;Jin-Qiang Hou;Jia-Heng Tan;Tian-Miao Ou;Ding Li;L. Gu;Zhishu Huang
设计、合成并评价了一系列异卡因地高酮及其类似物作为胆碱酯酶(Ches)和自身诱导的β-淀粉样蛋白(A-β)聚集的双重抑制剂。合成的化合物对胆碱酯酶抑制的IC50值在微纳摩尔范围内，部分化合物对胆碱酯酶具有较强的抑制活性和较高的选择性，明显优于本课题组报道的异地高酮类化合物。这些化合物中的大多数显示出比参考化合物姜黄素更强的自诱导Aβ聚集抑制活性。构效关系研究表明，与BuChE相比，对AChE具有较高抑制活性的衍生物对AChE也具有较高的选择性。用CD、EM、分子对接和动力学方法进一步研究了化合物6c对AChE和自诱导Aβ聚集的抑制作用。
A series of isaindigotone derivatives and analogues were designed, synthesized and evaluated as dual inhibitors of cholinesterases (ChEs) and self-induced β-amyloid (Aβ) aggregation. The synthetic compounds had IC50values 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 Aβ 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 Aβ aggregation was further studied using CD, EM, molecular docking and kinetics.