Cadinane- and drimane-type sesquiterpenoids produced by Paecilomyces sp. TE-540, an endophyte from Nicotiana tabacum L., are acetylcholinesterase inhibitors

被引：18

作者：

Xu, Kuo ^{[1
]}

Zhou, Qi ^{[2
]}

Li, Xiu-Qi ^{[1
,3
]}

Luo, Tian ^{[1
]}

Yuan, Xiao-Long ^{[1
]}

Zhang, Zhong-Feng ^{[1
]}

Zhang, Peng ^{[1
]}

机构：

[1] Chinese Acad Agr Sci, Tobacco Res Inst, Qingdao 266101, Peoples R China

[2] Hubei Univ Chinese Med, Wuhan 430070, Peoples R China

[3] Chinese Acad Agr Sci, Grad Sch, Beijing 100081, Peoples R China

来源：

BIOORGANIC CHEMISTRY | 2020年 / 104卷

基金：

中国国家自然科学基金;

关键词：

Paecilomyces; Nicotiana tabacum; Cadinane; Drimane; Acetylcholinesterase;

D O I：

10.1016/j.bioorg.2020.104252

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

Sesquiterpenoids with diverse skeleton types are regarded as potential lead compounds in pharmacological and other applications. Herein, we report the discovery of two new cadinane-type sesquiterpenoids, paecilacadinol A (1) and B (2); two new drimane-type sesquiterpenoids, ustusol D (3) and ustusol E (4); and six known analogs (5-10) from the endophytic fungus Paecilomyces sp. TE-540, enriching the structural diversity of naturally occurring sesquiterpenoids. Their planar structures were determined on the basis of detailed interpretation of 1D and 2D NMR spectroscopy and HRESIMS data, while their stereochemical structures were established by X-ray crystallographic analyses for 1 and 3-8 and theoretical calculations for 2. Notably, compounds 1 and 2 represent novel examples of cadinane-type sesquiterpenoids with ether bonds formed by intramolecular dehydration. Compounds 5 and 6 showed moderate activities against acetylcholinesterase (AChE), with IC50 values of 43.02 +/- 6.01 and 35.97 +/- 2.12 mu M, respectively. Docking analysis predicted that 5 bound well in the catalytic pocket of AChE via hydrophobic interactions with Trp84, Gly117, Ser122, and Tyr121 residues, while 6 was located with Asp72 and Ser122 residues.

引用

页数：8