Euchrestifolines A–O, fifteen novel carbazole alkaloids with potent anti-ferroptotic activity from Murraya euchrestifolia

IF 4.8 3区化学 Q1 CHEMISTRY, MEDICINAL

Natural Products and Bioprospecting Pub Date : 2025-01-02 DOI:10.1007/s13659-024-00483-7

Yue-Mei Chen, Nan-Kai Cao, Si-Si Zhu, Meng Ding, Hai-Zhen Liang, Ming-Bo Zhao, Ke-Wu Zeng, Peng-Fei Tu, Yong Jiang

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Abstract

Fifteen novel carbazole alkaloids, euchrestifolines A–O (1–15), were obtained from Murraya euchrestifolia. Their structures were elucidated by spectroscopic analysis, Mosher’s ester, calculated ECD, and transition metal complex ECD methods. Notably, euchrestifolines A–C (1–3) are the first naturally occurring pyrrolidone carbazoles to be identified, while euchrestifolines D–F (4–6) represent rare carbazole alkaloids containing a phenylpropanyl moiety; euchrestifoline G (7) features a unique benzopyranocarbazole skeleton. More importantly, these compounds exhibited significant anti-ferroptotic activity, along with inhibitory effects of nitric oxide (NO) production and notable cytotoxicity. This study marks the first disclosure of carbazole's inhibitory effects against ferroptosis, and the EC₅₀ values of some carbazoles ranging from 0.04 to 1 μM, substantially lower than the positive control, ferrostatin-1. In sum, this research not only enhances our understanding of carbazole alkaloids but also opens new avenues for the discovery of ferroptosis-related leading compounds.

Graphical abstract

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赤芍中15种新型咔唑类生物碱，具有较强的抗嗜铁活性

从木犀草中分离得到15个新的咔唑类生物碱，分别为木犀草碱A-O（1-15）。通过光谱分析、Mosher 's酯、计算ECD和过渡金属配合物ECD等方法对其结构进行了表征。值得注意的是，准赤霉素a - c（1-3）是第一个被鉴定的天然存在的吡咯烷酮类咔唑，而准赤霉素D-F（4-6）代表含有苯丙基部分的稀有咔唑类生物碱；euchrestifoline G(7)具有独特的苯并吡喃咔唑骨架。更重要的是，这些化合物表现出显著的抗铁腐活性，以及抑制一氧化氮（NO）的产生和显著的细胞毒性。本研究首次揭示了咔唑对铁下垂的抑制作用，部分咔唑的EC50值在0.04 ~ 1 μM之间，显著低于阳性对照铁抑素-1。总之，本研究不仅提高了我们对咔唑类生物碱的认识，而且为发现与铁中毒相关的先导化合物开辟了新的途径。图形抽象

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来源期刊

Natural Products and Bioprospecting CHEMISTRY, MEDICINAL-

CiteScore

8.30

自引率

2.10%

发文量

审稿时长

13 weeks

期刊介绍： Natural Products and Bioprospecting serves as an international forum for essential research on natural products and focuses on, but is not limited to, the following aspects: Natural products: isolation and structure elucidation Natural products: synthesis Biological evaluation of biologically active natural products Bioorganic and medicinal chemistry Biosynthesis and microbiological transformation Fermentation and plant tissue cultures Bioprospecting of natural products from natural resources All research articles published in this journal have undergone rigorous peer review. In addition to original research articles, Natural Products and Bioprospecting publishes reviews and short communications, aiming to rapidly disseminate the research results of timely interest, and comprehensive reviews of emerging topics in all the areas of natural products. It is also an open access journal, which provides free access to its articles to anyone, anywhere.