Surface Plasmon Resonance Guided Identification of Quinolone Alkaloids from the Fruits of Tetradium ruticarpum as FSP1 Inhibitors

IF 3.6 2区生物学 Q2 CHEMISTRY, MEDICINAL

Journal of Natural Products Pub Date : 2025-08-01 DOI:10.1021/acs.jnatprod.5c00595

Qi-Mei Tan, Mu Li, Jiang-Min Zhu, Bill Zhereng Liao, Ling-Yi Kong* and Jian-Guang Luo*,

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Abstract

Ferroptosis suppressor protein 1 (FSP1), a key regulator of ferroptosis that functions independently of glutathione, has become a vital therapeutic target in ferroptosis research. However, the discovery of FSP1 inhibitors remains a significant challenge, particularly given the absence of natural FSP1 inhibitors. In this study, surface plasmon resonance (SPR)-guided fractionation of the fruit extract of Tetradium ruticarpum (FTR) led to the isolation of 12 quinolone alkaloids, including ten known compounds (1–10) and two new ones (11 and 12). Compounds 1–9 all inhibited FSP1, among which 2–4 were the most potent (IC₅₀ = 0.47 ± 0.12, 0.29 ± 0.17, and 0.52 ± 0.98 μM, respectively), exceeding the positive control icFSP by more than 50-fold. This study represents the first identification of natural FSP1 inhibitors. Our findings highlight the potential of quinolone alkaloids as novel agents targeting FSP1 and underscore the importance of exploring natural products for the development of new ferroptosis modulators.

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表面等离激元共振引导下鉴定龙柏果实中喹诺酮类生物碱为FSP1抑制剂。

铁下垂抑制蛋白1 （Ferroptosis suppressor protein 1, FSP1）是一种独立于谷胱甘肽起作用的铁下垂关键调控因子，已成为铁下垂研究中重要的治疗靶点。然而，FSP1抑制剂的发现仍然是一个重大挑战，特别是在缺乏天然FSP1抑制剂的情况下。本研究利用表面等离子体共振（SPR）技术对四合金（Tetradium ruticarpum， FTR）果实提取物进行分离，分离得到12个喹诺酮类生物碱，包括10个已知化合物（1-10）和2个新化合物（11和12）。化合物1 ~ 9对FSP1均有抑制作用，其中2 ~ 4对FSP1的抑制作用最强（IC50分别为0.47±0.12 μM、0.29±0.17 μM和0.52±0.98 μM），均超过阳性对照icFSP的50倍以上。这项研究首次发现了天然的FSP1抑制剂。我们的研究结果强调了喹诺酮类生物碱作为针对FSP1的新型药物的潜力，并强调了探索天然产物对开发新的铁下垂调节剂的重要性。

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.