Synthesis and evaluation of novel rutaecarpine derivatives and related alkaloids derivatives as selective acetylcholinesterase inhibitors

被引：54

作者：

Wang, Bin ^{[1
,2
]}

Mai, Yi-Chi ^{[1
]}

Li, Yue ^{[1
]}

Hou, Jin-Qiang ^{[1
]}

Huang, Shi-Liang ^{[1
]}

Ou, Tian-Miao ^{[1
]}

Tan, Jia-Heng ^{[1
]}

An, Lin-Kun ^{[1
]}

Li, Ding ^{[1
]}

Gu, Lian-Quan ^{[1
]}

Huang, Zhi-Shu ^{[1
]}

机构：

[1] Sun Yat Sen Univ, Sch Pharmaceut Sci, Guangzhou 510006, Guangdong, Peoples R China

[2] Xiangnan Univ, Dept Chem & Life Sci, Chenzhou 423000, Hunan, Peoples R China

来源：

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY | 2010年 / 45卷 / 04期

关键词：

Rutaecarpine derivatives; Acetylcholinesterase inhibitors; Synthesis; Selectivity; ALZHEIMERS-DISEASE; EVODIA-RUTAECARPA; BUTYRYLCHOLINESTERASE; DEHYDROEVODIAMINE; OXOISOAPORPHINE; BINDING;

D O I：

10.1016/j.ejmech.2009.12.044

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

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.

引用

页码：1415 / 1423

页数：9

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