New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti

Natural Products and Bioprospecting

Original Article

Yonghui Zhang¹  Jianping Wang¹  Zhihong Huang¹  Ziming Zhao¹  Zi Ye¹  Shuyuan Mo¹  Wanqi Yang¹  Zhengxi Hu¹  Yaxin Zhang¹ 

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

关键词: Hypericum beanii;    Root soil-derived fungus;    Penicillium roqueforti;    Structural elucidation;    Cytotoxicity;   

DOI  :  10.1007/s13659-023-00381-4

 received in 2023-04-13, accepted in 2023-05-20,  发布年份 2023

来源: Springer

【 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. Compound 1 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 compound 2 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 compound 1 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 for 1 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, compound 1 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 compound 1 significantly induced cell cycle arrest in Farage and SU-DHL-2 cells by causing abnormal ROS level and triggering oxidative stress.Graphical Abstract

【 授权许可】

CC BY   
© The Author(s) 2023

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