Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways

doi:10.1007/s13659-025-00498-8

应用天然产物 ›› 2025, Vol. 15 ›› Issue (2): 17-17.DOI: 10.1007/s13659-025-00498-8

Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways

Pengkun Li¹, Qin Li¹, Aimin Fu¹, Yang Xiao¹, Chunmei Chen¹, Hucheng Zhu¹, Changxing Qi¹, Wei Wei², Yuan Zhou¹, Yonghui Zhang¹

1. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China;
2. China National Center for Biotechnology Development, Beijing, 100039, People's Republic of China

收稿日期:2025-01-06 接受日期:2025-02-14 出版日期:2025-04-25 发布日期:2025-05-17
通讯作者: Wei Wei, E-mail:weiwei@cncbd.org.cn;Yuan Zhou, E-mail:zhouyuan@hust.edu.cn;Yonghui Zhang, E-mail:zhangyh@mails.tjmu.edu.cn
基金资助:
National Natural Science Foundation of China (U22A20380, 82173706, 82104028) and Fundamental Research Funds for the Central Universities (2024BRA018) financially supported this project.

Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways

Pengkun Li¹, Qin Li¹, Aimin Fu¹, Yang Xiao¹, Chunmei Chen¹, Hucheng Zhu¹, Changxing Qi¹, Wei Wei², Yuan Zhou¹, Yonghui Zhang¹

1. Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, People's Republic of China;
2. China National Center for Biotechnology Development, Beijing, 100039, People's Republic of China

Received:2025-01-06 Accepted:2025-02-14 Online:2025-04-25 Published:2025-05-17
Contact: Wei Wei, E-mail:weiwei@cncbd.org.cn;Yuan Zhou, E-mail:zhouyuan@hust.edu.cn;Yonghui Zhang, E-mail:zhangyh@mails.tjmu.edu.cn
Supported by:
National Natural Science Foundation of China (U22A20380, 82173706, 82104028) and Fundamental Research Funds for the Central Universities (2024BRA018) financially supported this project.

摘要/Abstract

摘要： Five novel emestrin-type epipolythiodioxopiperazines (ETPs), prenylemestrins C-G (1-5), along with two known ETPs, prenylemestrin A (6) and prenylemestrin B (7), were obtained from Aspergillus nidulans. Their structures were characterized by spectroscopic data, X-ray crystallographic data, ECD comparisons and calculations. Prenylemestrins C-G (1 - 5) represent a rare class of ETPs, characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety. Notably, compound 6 exhibited moderate cytotoxicity, inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.

关键词: Aspergillus nidulans, Epipolythiodioxopiperazines, Thioethanothio bridge, Structural elucidation, Cytotoxicity

Abstract: Five novel emestrin-type epipolythiodioxopiperazines (ETPs), prenylemestrins C-G (1-5), along with two known ETPs, prenylemestrin A (6) and prenylemestrin B (7), were obtained from Aspergillus nidulans. Their structures were characterized by spectroscopic data, X-ray crystallographic data, ECD comparisons and calculations. Prenylemestrins C-G (1 - 5) represent a rare class of ETPs, characterized by a 2,5-dithia-7,9-diazabicyclo[4.2.2]decane-8,10-dione core involving a hemiterpene moiety. Notably, compound 6 exhibited moderate cytotoxicity, inducing G2/M cell cycle arrest and apoptosis of L1210 cells by regulating the PI3K/AKT signaling pathway and mitochondrial apoptotic mechanisms.

Key words: Aspergillus nidulans, Epipolythiodioxopiperazines, Thioethanothio bridge, Structural elucidation, Cytotoxicity

Pengkun Li, Qin Li, Aimin Fu, Yang Xiao, Chunmei Chen, Hucheng Zhu, Changxing Qi, Wei Wei, Yuan Zhou, Yonghui Zhang. Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways[J]. 应用天然产物, 2025, 15(2): 17-17.

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Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways

Emestrin-type epipolythiodioxopiperazines from Aspergillus nidulans with cytotoxic activities by regulating PI3K/AKT and mitochondrial apoptotic pathways

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