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<p>Fifteen novel carbazole alkaloids, euchrestifolines A–O (<b>1</b>–<b>15</b>), were obtained from <i>Murraya euchrestifolia</i>. Their structures were elucidated by spectroscopic analysis, Mosher’s ester, calculated ECD, and transition metal complex ECD methods. Notably, euchrestifolines A–C (<b>1</b>–<b>3</b>) are the first naturally occurring pyrrolidone carbazoles to be identified, while euchrestifolines D–F (<b>4</b>–<b>6</b>) represent rare carbazole alkaloids containing a phenylpropanyl moiety; euchrestifoline G (<b>7</b>) 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 EC<sub>50</sub> values of some carbazoles ranging from 0.04 to 1&#xa0;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.</p> Graphical abstract <p></p>

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

  • 期刊论文

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  • 发表日期：

    2025年1月2日

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  • 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

摘要

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