Talarotetramates A-F, Decalin-Containing Tetramic Acids as Ferroptosis Inhibitors from the Deep-Sea-Derived Fungus Talaromyces sp. gb505.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-07-05 DOI:10.1021/acs.jnatprod.5c00679

Wenjing Tian, Xuan Chen, Gaiyun Zhang, Linfeng Gong, Junxiong Lin, Bihong Hong, Lisheng Li, Siwen Niu

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引用次数: 0

Abstract

Talarotetramates A-F (1-6), six novel 3-decalinoyltetramic acids (3-DTAs), were discovered from the deep-sea-derived fungus Talaromyces sp. gb505, along with a structurally related analogue, talaroconvolutin A (7). Their structures were elucidated by comprehensive analysis of NMR spectra, HRESIMS, and quantum chemical calculations of ECD and NMR data. Compounds 1-4 represent the first examples of unique 3-DTA heterodimers, formed via intermolecular ketalization between talaroconvolutin-type 3-DTAs and a C₁₀ polyketide. Compound 5 is the first nor-talaroconvolutin-type 3-DTA with the reduction of the para-hydroxybenzyl, while 6 contains a unique epoxy ring system, unprecedented in 3-DTAs. We discovered for the first time that compounds 6 and 7 exhibit inhibitory activity against RSL3-induced ferroptosis. Notably, 6 exhibited potent ferroptosis inhibition with an EC₅₀ value of 7.77 μM. Mechanistic investigations indicate that 6 suppresses ferroptosis by alleviating lipid peroxidation and upregulating NRF2 expression. The present work provides new insights into the structural diversity and pharmaceutical potential of 3-DTAs.

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深海源真菌Talaromyces sp. [gb505]中含十calin的四羧酸类铁沉抑制剂Talarotetramates A-F。

Talarotetramates a- f（1-6）是从深海真菌Talaromyces sp. gb505中发现的6种新型3-decalinoyltetramic酸（3-DTAs），以及结构相关的类似物talaroconvolutin a(7)。通过核磁共振光谱、hremsims、ECD和核磁共振数据的量子化学计算等综合分析，对它们的结构进行了鉴定。化合物1-4是独特的3-DTA异源二聚体的第一个例子，它是通过talaroconvolutin型3-DTA和C10聚酮之间的分子间酮化形成的。化合物5是首个通过对羟基苯基还原而得到的非塔拉罗旋曲素型3-DTA，而化合物6含有独特的环氧环体系，这在3-DTA中是前所未有的。我们首次发现化合物6和7对rsl3诱导的铁下垂具有抑制活性。值得注意的是，其中6个表现出明显的铁下垂抑制作用，EC50值为7.77 μM。机制研究表明，6通过减轻脂质过氧化和上调NRF2表达来抑制铁下垂。本工作为3- dta的结构多样性和药物潜力提供了新的见解。

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.