New secondary metabolites with cytotoxicity from fungus Penicillium roqueforti  

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

机构地区：[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,China

出　　处：《Natural Products and Bioprospecting》2023年第1期577-584,共8页应用天然产物（英文）

基　　金：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);the Chinese Medicine Research Foundation of Health Commission of Hubei Province(No.ZY2021Z019).

摘　　要：Two novel compounds including a cyclohelminthol type polyketide(namely oxaleimide K,1)and a maleimide deriva-tive(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 For-estry 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 tetrahydro-furan 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(IC_(50)<20μM,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.

关 键 词：Hypericum beanii N.Robson Root soil-derived fungus Penicillium roqueforti Structural elucidation CYTOTOXICITY 

分 类 号：O62[理学—有机化学]