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

doi:10.1007/s13659-024-00483-7

Natural Products and Bioprospecting ›› 2025, Vol. 15 ›› Issue (1): 5-5.DOI: 10.1007/s13659-024-00483-7

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

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

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China

Received:2024-08-31 Accepted:2024-11-10 Online:2025-02-15 Published:2025-02-24
Contact: Yong JIANG,E-mail:yongjiang@bjmu.edu.cn
Supported by:
We express our gratitude to the National Natural Science Foundation of China (NSFC) for their financial support through grant numbers 81973199, 82173949, U23A20514, 81773864, and 81473106. Additionally, we acknowledge the funding provided by the Key Research and Development Project of Shandong Province (2021CXGC010507). Thanks to Mr. Cao Fei from Hebei University for his help in quantum chemical calculations.

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

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

State Key Laboratory of Natural and Biomimetic Drugs, School of Pharmaceutical Sciences, Peking University, Beijing, 100191, People’s Republic of China

通讯作者: Yong JIANG,E-mail:yongjiang@bjmu.edu.cn
基金资助:
We express our gratitude to the National Natural Science Foundation of China (NSFC) for their financial support through grant numbers 81973199, 82173949, U23A20514, 81773864, and 81473106. Additionally, we acknowledge the funding provided by the Key Research and Development Project of Shandong Province (2021CXGC010507). Thanks to Mr. Cao Fei from Hebei University for his help in quantum chemical calculations.

Abstract

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.

Key words: NO inhibition, Cytotoxicity, Murraya euchrestifolia, Carbazole, Benzopyranocarbazole, Anti-ferroptosis

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.

关键词: Murraya euchrestifolia, Carbazole, Benzopyranocarbazole, Anti-ferroptosis, NO inhibition, Cytotoxicity

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. Euchrestifolines A-O, fifteen novel carbazole alkaloids with potent anti-ferroptotic activity from Murraya euchrestifolia[J]. Natural Products and Bioprospecting, 2025, 15(1): 5-5.

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

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

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