Cytochalasins from the Sponge-Derived Fungus Aspergillus templicola and Their Biological Activities.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-06-05 DOI:10.1021/acs.jnatprod.5c00180

Kai Li, Yue Zhang, Tianyun Jin, Lei Li, Junjie Yang, Sen Wang, Cili Wang, Pinglin Li

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Abstract

Guided by biosynthetic gene cluster analysis, fractionation of the fermentation extract of Aspergillus templicola from the sponge Agelas sp. led to the isolation of nine new cytochalasins, named colachalasins A-I (1-9), along with four known cytochalasins (10-13). The structures of 1-9 were elucidated using spectroscopic data and single-crystal X-ray diffraction. Structurally, compound 2 is characterized by an open 12-carbon chain unprecedented among the cytochalasins. Compounds 1-3 demonstrated moderate protective effects against alcohol-induced hepatic damage in zebrafish assays. Compound 11 exhibited potent anti-inflammatory activity by inhibiting the expression of IKKβ, STAT3, TNF-α, IL-1β, NF-κB, NLRP3, IL-6, and MyD88 while enhancing the expression of IL-4 and Nrf2 in zebrafish assays. Additionally, compound 7 showed significant cytotoxicity against NCI-H446 cell lines, with an IC₅₀ value of 0.67 μM, and induced apoptosis in a dose-dependent manner.

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海绵来源真菌天曲曲霉细胞松弛素及其生物活性研究。

在生物合成基因聚类分析的指导下，从海绵Agelas sp.中分离出templicola Aspergillus templicola发酵提取物，分离出9个新的细胞松弛素，命名为colachalasins A-I(1-9)，以及4个已知的细胞松弛素（10-13）。利用光谱数据和单晶x射线衍射对1-9的结构进行了分析。在结构上，化合物2的特点是一个开放的12碳链在细胞松弛素中是前所未有的。在斑马鱼试验中，化合物1-3显示出对酒精引起的肝损伤的中度保护作用。在斑马鱼实验中，化合物11通过抑制IKKβ、STAT3、TNF-α、IL-1β、NF-κB、NLRP3、IL-6和MyD88的表达，同时增强IL-4和Nrf2的表达，显示出强大的抗炎活性。此外，化合物7对NCI-H446细胞株具有显著的细胞毒性，IC50值为0.67 μM，并呈剂量依赖性诱导细胞凋亡。

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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.