Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors
Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors
复制标题
新型吴茱萸碱衍生物及相关生物碱衍生物作为选择性乙酰胆碱酯酶抑制剂的合成与评价
DOI：
10.1016/j.ejmech.2009.12.044
复制
发表时间：
2010-04-01
影响因子：
6.7
通讯作者：
Huang, Zhi-Shu
中科院分区：
文献类型：
--
作者：
Wang, Bin;Mai, Yi-Chi;Huang, Zhi-Shu
合成了一系列新的芦果卡尔松衍生物及其相关生物碱衍生物- 3-氨基氨基取代芦果卡尔松4a-f、7,8-脱氢芦果卡尔松5a-c和6-氨基氨基取代3-[2-（3-吲哚基）乙基]-4(3a)-喹唑啉酮8a-c，并作为乙酰胆碱酯酶（AChE）抑制剂进行药理学评价。合成的化合物对AChE具有较强的抑制活性，对AChE对BuChE具有较高的选择性。讨论了它们的构效关系，并通过动力学表征和分子对接研究进一步阐明了它们的结合构象和同时相互作用模式。(C) 2009 Elsevier Masson SAS。版权所有。
A series of novel rutaecarpine derivatives and related alkaloid derivatives 3-aminoalkanamido-substituted rutaecarpine 4a-f and 7,8-dehydrorutaecarpine 5a-c, and 6-aminoalkanamido-substituted 3-[2-(3-Indolyl)ethyl]-4(3a)-quinazolinones 8a-c, were synthesized and subjected to pharmacological evaluation as acetylcholinesterase (AChE) inhibitors. The synthetic compounds exhibited strong inhibitory activity for AChE and high selectivity for AChE over BuChE. The structure-activity relationships were discussed and their binding conformation and simultaneous interactions mode were further clarified by kinetic characterization and the molecular docking studies. (C) 2009 Elsevier Masson SAS. All rights reserved.