New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus,Organic & Biomolecular Chemistry

当前位置： X-MOL 学术 › Org. Biomol. Chem. › 论文详情

Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)

New 3,5-dimethylorsellinic acid-based meroterpenoids with BACE1 and AchE inhibitory activities from Aspergillus terreus
Organic & Biomolecular Chemistry ( IF 2.9 ) Pub Date : 2018-11-07 , DOI: 10.1039/c8ob02741b
Changxing Qi _{1,

2,

3,

4,

5} , Yuben Qiao _{1,

2,

3,

4,

5} , Weixi Gao _{1,

2,

3,

4,

5} , Mengting Liu _{1,

2,

3,

4,

5} , Qun Zhou _{1,

2,

3,

4,

5} , Chunmei Chen _{1,

2,

3,

4,

5} , Yongji Lai _{6,

7,

8,

9} , Yongbo Xue _{1,

2,

3,

4,

5} , Jinwen Zhang _{3,

4,

5,

6,

10} , Dongyan Li _{3,

4,

5,

6,

10} , Jianping Wang _{1,

2,

3,

4,

5} , Hucheng Zhu _{1,

2,

3,

4,

5} , Zhengxi Hu _{1,

2,

3,

4,

5} , Yuan Zhou _{1,

2,

3,

4,

5} , Yonghui Zhang _{1,

2,

3,

4,

5}

Affiliation

Chemical investigation of the extracts of Aspergillus terreus resulted in the identification of terreusterpenes A–D (1–4), four new 3,5-dimethylorsellinic acid-based meroterpenoids. The structures and absolute configurations of 1–4 were elucidated by spectroscopic analyses including HRESIMS and 1D- and 2D-NMR, chemical conversion, and single crystal X-ray diffraction. Terreusterpenes A (1) and B (2) featured 2,3,5-trimethyl-4-oxo-5-carboxy tetrahydrofuran moieties. Terreusterpene D (4) was characterized by a 4-hydroxy-3-methyl gamma lactone fragment that was generated by accident from the rearrangement of 3 in a mixed tetrahydrofuran–H₂O–MeOH solvent. All these compounds were evaluated for the β-site amyloid precursor protein-cleaving enzyme 1 (BACE1) and acetylcholinesterase (AchE) inhibitory activities. Among them, compounds 1 and 2 showed potentially significant BACE1 inhibitory activity, with IC₅₀ values of 5.98 and 11.42 μM, respectively. Interestingly, compound 4 exhibited promising BACE1 and AchE inhibitory activities, with IC₅₀ values of 1.91 and 8.86 μM, respectively, while 3 showed no such activity. Taken together, terreusterpenes A and B could be of great importance for the development of new BACE1 inhibitors, while terreusterpene D could serve as the first dual-targeted 3,5-dimethylorsellinic acid-based meroterpenoid for the treatment of Alzheimer's disease.

中文翻译：

新的基于3,5-二甲基熊果酸的类萜类化合物具有曲霉曲霉的BACE1和AchE抑制活性

对土壤曲霉提取物的化学研究导致鉴定出萜类戊二烯A–D（1-4），四种新的基于3,5-二甲基熊果酸的类萜。通过光谱分析（包括HRESIMS以及1D和2D-NMR，化学转化和单晶X射线衍射）阐明了1–4的结构和绝对构型。萜类萜A（1）和B（2）具有2,3,5-三甲基-4-氧代-5-羧基四氢呋喃部分。Terreusterpene D（4）的特征是4-羟基-3-甲基γ内酯片段，该片段是由混合四氢呋喃–H ₂中3的重排意外产生的。O–MeOH溶剂。对所有这些化合物的β位淀粉样蛋白前体蛋白裂解酶1（BACE1）和乙酰胆碱酯酶（AchE）抑制活性进行了评估。其中，化合物1和2具有潜在的显着BACE1抑制活性，IC ₅₀值分别为5.98和11.42μM。有趣的是，化合物4表现出有希望的BACE1和AchE抑制活性，IC ₅₀值分别为1.91和8.86μM，而化合物3显示没有这样的活动。综上所述，萜烯戊二烯A和B对于开发新的BACE1抑制剂可能具有重要意义，而萜烯丙二烯D可以作为首个基于双靶向3,5-二甲基熊果酸的类萜类化合物治疗阿尔茨海默氏病。

更新日期：2018-11-28

点击分享查看原文

点击收藏

阅读更多本刊新发论文本刊介绍/投稿指南