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结节孢绿菌素A - H,来自结节孢属的生物活性绿菌素

Nodulisporiviridins A-H, Bioactive Viridins from Nodulisporium sp.

作者信息

Zhao Qin, Chen Guo-Dong, Feng Xiao-Lin, Yu Yang, He Rong-Rong, Li Xiao-Xia, Huang Yan, Zhou Wen-Xia, Guo Liang-Dong, Zheng Yi-Zhi, Yao Xin-Sheng, Gao Hao

机构信息

†Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy, Jinan University, Guangzhou 510632, People's Republic of China.

‡State Key Laboratory of Toxicology and Medical Countermeasures, Beijing Institute of Pharmacology and Toxicology, Beijing 100850, People's Republic of China.

出版信息

J Nat Prod. 2015 Jun 26;78(6):1221-30. doi: 10.1021/np500912t. Epub 2015 May 15.

Abstract

Eight new viridins, nodulisporiviridins A-H (1-8), were isolated from the extract of an endolichenic fungal strain Nodulisporium sp. (No. 65-17-2-1) that was fermented with potato-dextrose broth. The structures were determined using spectroscopic and X-ray crystallographic analysis. Nodulisporiviridins A-D (1-4) are unique viridins with an opened ring A. The Aβ42 aggregation inhibitory activities of 1-8 were evaluated using a thioflavin T (ThT) assay with epigallocatechin gallate (EGCG) as the positive control (EGCG IC50 of 0.5 μM). Nodulisporiviridin G (7) displayed potent inhibitory activity with an IC50 value of 1.2 μM, and the preliminary trend of activity of these viridins as Aβ42 aggregation inhibitors was proposed. The short-term memory assay on an Aβ transgenic drosophila model of Alzheimer's disease showed that all eight compounds improved the short-term memory capacity, with potencies close to that of the positive control (memantine).

摘要

从一株用马铃薯葡萄糖肉汤发酵的内生地衣真菌菌株Nodulisporium sp.(编号65 - 17 - 2 - 1)的提取物中分离出8种新的绿菌素,即节菱孢绿菌素A - H(1 - 8)。通过光谱和X射线晶体学分析确定了它们的结构。节菱孢绿菌素A - D(1 - 4)是具有开环A的独特绿菌素。以表没食子儿茶素没食子酸酯(EGCG)为阳性对照(EGCG的IC50为0.5 μM),采用硫黄素T(ThT)分析法评估了1 - 8对Aβ42聚集的抑制活性。节菱孢绿菌素G(7)表现出强效抑制活性,IC50值为1.2 μM,并提出了这些绿菌素作为Aβ42聚集抑制剂的初步活性趋势。在阿尔茨海默病的Aβ转基因果蝇模型上进行的短期记忆试验表明,所有这8种化合物都提高了短期记忆能力,效力与阳性对照(美金刚)相近。

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