Asperdoles A-N: Indole Diterpenoids from the Endolichenic Fungus Aspergillus sp. TJ403-YJ22.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-06-27 Epub Date: 2025-05-28 DOI:10.1021/acs.jnatprod.5c00224

Jun Yao, Chenyang Wang, Hanxiao Zeng, Yu Cao, Xianjie Qiu, Wenqi Li, Yongzhi Lu, Jinsai Shang, Jianping Wang, Yonghui Zhang, Zhengxi Hu

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引用次数: 0

Abstract

Fourteen new indole diterpenoids, designated as asperdoles A-N (1-14), were isolated from the endolichenic fungus Aspergillus sp. TJ403-YJ22. Notably, compounds 1-7 were characterized by the presence of 2-keto-3-hydroxy-oxidized indole moieties, which were connected to diterpenoid segments via methylene bridges. Compounds 1-5 featured fused 6/6/6 ring diterpenoid frameworks, whereas the tetrahydropyran in compounds 6-14 was cleaved, resulting in the formation of terminal vicinal diols in compounds 6-12 and olefinic double bonds in compounds 13 and 14. The planar structures and absolute configurations of these compounds were elucidated through a combination of NMR spectroscopy, HRESIMS, Snatzke's method, single-crystal X-ray diffraction analysis, and ECD calculations. Compound 4 exhibited selective FXR agonistic activity, with an EC₅₀ value of 4.1 ± 0.3 μM, suggesting its potential therapeutic application in the treatment of cholestasis.

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曲霉A-N：曲霉内生真菌中的吲哚二萜类化合物。

从内生真菌曲霉（Aspergillus sp. TJ403-YJ22）中分离到14个新的吲哚二萜，编号为曲霉A-N（1-14）。值得注意的是，化合物1-7的特点是存在2-酮-3-羟基氧化吲哚基团，它们通过亚甲基桥连接到二萜段。化合物1-5具有融合的6/6/6环二萜框架，而化合物6-14的四氢吡喃被劈裂，导致化合物6-12形成末端邻二醇，化合物13和14形成烯烃双键。通过核磁共振光谱、hresms、Snatzke方法、单晶x射线衍射分析和ECD计算，对这些化合物的平面结构和绝对构型进行了分析。化合物4表现出选择性的FXR激动作用，EC50值为4.1±0.3 μM，提示其在胆汁淤积症的治疗中具有潜在的应用前景。

本文章由计算机程序翻译，如有差异，请以英文原文为准。

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来源期刊

Journal of Natural Products 生物-药学

CiteScore

9.10

自引率

5.90%

发文量

294

审稿时长

2.3 months

期刊介绍： The Journal of Natural Products invites and publishes papers that make substantial and scholarly contributions to the area of natural products research. Contributions may relate to the chemistry and/or biochemistry of naturally occurring compounds or the biology of living systems from which they are obtained. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin. When new compounds are reported, manuscripts describing their biological activity are much preferred. Specifically, there may be articles that describe secondary metabolites of microorganisms, including antibiotics and mycotoxins; physiologically active compounds from terrestrial and marine plants and animals; biochemical studies, including biosynthesis and microbiological transformations; fermentation and plant tissue culture; the isolation, structure elucidation, and chemical synthesis of novel compounds from nature; and the pharmacology of compounds of natural origin.