Neuroprotective Indole Alkaloids from the Soil-Derived Fungus Trichocladium sp. XZ8.

IF 3.3 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-01-24 Epub Date: 2025-01-11 DOI:10.1021/acs.jnatprod.4c01250

Xiao-Qi Duan, Xin-Yu Wang, Huai-Chang Qi, Yi-Jie Zhai, Wen-Bo Han

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引用次数: 0

Abstract

A chemical investigation of the soil-derived fungus Trichocladium sp. XZ8 led to the isolation of five new indole alkaloids, trichindoles A-E (1-5), with diverse architectures, along with seven known analogues (6-12). Their structures were elucidated by extensive spectroscopic data analysis, and their absolute configurations were determined by single-crystal X-ray diffraction and modified Mosher's method. Compound 1 is a polyketide-alkaloid hybrid incorporating a rare succinimide motif, and compound 2 represents the first example of a dimeric isopentenyl indole-containing alkaloid bridged by a propane-1,2-diol moiety. Compounds 1, 4, 8, 11, and 12 showed significant neuroprotective effects against RSL3-induced ferroptosis in PC12 cells at 10 μM. Moreover, 1 and 4 might ameliorate RSL3-induced ferroptosis through the regulation of the SLC7A11 pathway and ferritinophagy, suggesting their potential as promising lead compounds for the treatment of neurodegenerative diseases.

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土源真菌Trichocladium sp. XZ8中神经保护吲哚类生物碱。

对源自土壤的真菌Trichocladium sp. XZ8进行化学研究，分离出5种结构多样的吲哚类生物碱，trichindoles A- e(1-5)，以及7种已知的类似物（6-12）。通过广泛的光谱数据分析确定了它们的结构，并通过单晶x射线衍射和改进的Mosher法确定了它们的绝对构型。化合物1是含有罕见琥珀酰亚胺基序的聚酮-生物碱杂化物，化合物2是由丙烷-1,2-二醇基段桥接的含二聚异戊基吲哚的生物碱的第一个例子。化合物1、4、8、11和12对10 μM rsl3诱导的PC12细胞铁下垂具有显著的神经保护作用。此外，1和4可能通过调节SLC7A11通路和铁蛋白自噬来改善rsl3诱导的铁下垂，这表明它们有可能成为治疗神经退行性疾病的有希望的先导化合物。

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.