New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

doi:10.1007/s13659-023-00381-4

应用天然产物 ›› 2023, Vol. 13 ›› Issue (3): 17-17.DOI: 10.1007/s13659-023-00381-4

New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

Shuyuan Mo, Ziming Zhao, Zi Ye, Zhihong Huang, Yaxin Zhang, Wanqi Yang, Jianping Wang, Zhengxi Hu, Yonghui Zhang

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

收稿日期:2023-04-13 出版日期:2023-06-24 发布日期:2023-07-18
通讯作者: Jianping Wang,E-mail:jpwang1001@163.com;Zhengxi Hu,E-mail:hzx616@126.com;Yonghui Zhang,E-mail:zhangyh@mails.tjmu.edu.cn
基金资助:
This project was financially supported by the National Program for Support of Top-notch Young Professionals (No. 0106514050), the National Natural Science Foundation of China (Nos. 82273811 and 31870326), the National Key R&D Program of China (No. 2021YFA0910500), the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005), the Research and Development Program of Hubei Province (No. 2020BCA058), and the Chinese Medicine Research Foundation of Health Commission of Hubei Province (No. ZY2021Z019).

New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

Shuyuan Mo, Ziming Zhao, Zi Ye, Zhihong Huang, Yaxin Zhang, Wanqi Yang, Jianping Wang, Zhengxi Hu, Yonghui Zhang

Hubei Key Laboratory of Natural Medicinal Chemistry and Resource Evaluation, School of Pharmacy, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, 430030, China

Received:2023-04-13 Online:2023-06-24 Published:2023-07-18
Contact: Jianping Wang,E-mail:jpwang1001@163.com;Zhengxi Hu,E-mail:hzx616@126.com;Yonghui Zhang,E-mail:zhangyh@mails.tjmu.edu.cn
Supported by:
This project was financially supported by the National Program for Support of Top-notch Young Professionals (No. 0106514050), the National Natural Science Foundation of China (Nos. 82273811 and 31870326), the National Key R&D Program of China (No. 2021YFA0910500), the National Natural Science Foundation for Distinguished Young Scholars (No. 81725021), the Innovative Research Groups of the National Natural Science Foundation of China (No. 81721005), the Research and Development Program of Hubei Province (No. 2020BCA058), and the Chinese Medicine Research Foundation of Health Commission of Hubei Province (No. ZY2021Z019).

摘要/Abstract

摘要： Two novel compounds including a cyclohelminthol type polyketide (namely oxaleimide K,1) and a maleimide derivative (namely peniroquefortine A,2), and a new natural product (namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide,3), together with four known compounds (4-7), were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment. Compound1 represents the second example of a cyclohelminthol type polyketide, which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin (oct-1-en-3-yl) moiety, and compound2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds. Remarkably, the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound1 is determined by the single-crystal diffraction analysis for the first time, highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydrofuran moiety for1 rather than a Z-configuration as previously reported in the biosynthesis study, which gives a new insight into the structural elucidation of this category of polyketides. Additionally, compound1 exhibited significant cytotoxic activity against multiple tumor cells, especially against the Farage and SU-DHL-2 cells (IC₅₀<20 μM, 48 h). Further mechanism study revealed that compound1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.

关键词: Hypericum beanii N. Robson, Root soil-derived fungus, Penicillium roqueforti, Structural elucidation, Cytotoxicity

Abstract: Two novel compounds including a cyclohelminthol type polyketide (namely oxaleimide K,1) and a maleimide derivative (namely peniroquefortine A,2), and a new natural product (namely 2-(acetylamino)-N-[(1E)-2-phenylethenyl]-acetamide,3), together with four known compounds (4-7), were isolated and identified from fungus Penicillium roqueforti, which was separated from the root soil of Hypericum beanii N. Robson collected from the Shennongjia Forestry District, Hubei Province. Their structures including absolute configurations were mainly established by the NMR spectroscopy analyses and single-crystal X-ray diffraction experiment. Compound1 represents the second example of a cyclohelminthol type polyketide, which features a rare 6/6/5/5 tetracyclic system and a branched aliphatic chain containing a terminal olefin (oct-1-en-3-yl) moiety, and compound2 possesses an unprecedented carbon skeleton that is uniquely defined by a maleimide moiety linked to the respective 4-methylene-2-(3-methylbut-2-en-1-yl)-phenol and para-substituted aromatic moieties via the carbon-carbon bonds. Remarkably, the absolute configuration of a cyclohelminthol type polyketide as exemplified by compound1 is determined by the single-crystal diffraction analysis for the first time, highlighting an E-configuration for the linkage of a succinimide moiety and a tetrahydrofuran moiety for1 rather than a Z-configuration as previously reported in the biosynthesis study, which gives a new insight into the structural elucidation of this category of polyketides. Additionally, compound1 exhibited significant cytotoxic activity against multiple tumor cells, especially against the Farage and SU-DHL-2 cells (IC₅₀<20 μM, 48 h). Further mechanism study revealed that compound1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.

Key words: Hypericum beanii N. Robson, Root soil-derived fungus, Penicillium roqueforti, Structural elucidation, Cytotoxicity

Shuyuan Mo, Ziming Zhao, Zi Ye, Zhihong Huang, Yaxin Zhang, Wanqi Yang, Jianping Wang, Zhengxi Hu, Yonghui Zhang. New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti[J]. 应用天然产物, 2023, 13(3): 17-17.

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New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

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