Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products socia...Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.展开更多
目的 对从混合培养的海洋软珊瑚共附生真菌中获得的结构新颖、活性良好的杂萜类成分进行研究。方法采用大米培养基对2株软珊瑚共附生曲霉属真菌EGF7-0-1和EGF15-0-3进行共培养;根据杂萜类化合物的结构特征,在基于质谱的分子网络(GNPS)...目的 对从混合培养的海洋软珊瑚共附生真菌中获得的结构新颖、活性良好的杂萜类成分进行研究。方法采用大米培养基对2株软珊瑚共附生曲霉属真菌EGF7-0-1和EGF15-0-3进行共培养;根据杂萜类化合物的结构特征,在基于质谱的分子网络(GNPS)和薄层色谱(TLC)的共同指导下,运用多种柱色谱及高效液相色谱(HPLC)等方法对其杂萜类成分进行目标导向分离;通过核磁共振(NMR)、高分辨质谱(HRMS)和旋光(ORD)等技术及物理常数对照等手段对单体化合物进行结构鉴定;采用液相色谱质谱联用(LC-MS^(n))和GNPS技术分析比较获得的杂萜类成分在2株真菌共培养及EGF7-0-1单培养中的含量。结果 从2株海洋真菌Aspergillus sp. EGF7-0-1和EGF15-0-3共培养的大米培养基中共分离得到7个杂萜类化合物,结构分别为terretonin (1)、terretonin A (2)、terretonin D1 (3)、terretonin H (4)、terreustoxin E (5)、aperterpene N (6)和asperterpene J (7)。LC-MSn和GNPS分析结果表明共培养条件下杂萜类化合物更为丰富。结论 化合物1~7均为具6/6/6骈并骨架的3,5-二甲基苔色酸(DMOA)途径衍生而成的杂萜。与菌株EGF7-0-1单培养相比,2株真菌共培养可以诱导产生丰富的杂萜,为进一步新颖杂萜类化合物的挖掘提供支持数据。展开更多
基金supported by the National Natural Science Foundation of China(Nos.82273845,82304331,and 82360695)Guangxi Natural Science Foundation project(No.2023GXNSFBA026305).
文摘Hyperactivation of DNA repairing pathway is highly associated with the chemosensitivity and chemoresistance of cancer cells.In this manuscript,guided by cascaded one strain many compounds-global natural products social molecular networking(OSMAC-GNPS)strategy,a pair of epimeric environmental-induced metabolites were isolated from Aspergillus sp.EGF 15-0-3.Structurally,sterpiperazines A(1)and B(2)represent the first steroid-based indole alkaloids with unprecedented backbones.Biologically,compound 1 could be identified as a novel tyrosyl-DNA phosphodiesterase 1(Tdp1)inhibitor with a unique mechanism distinct from the reported modulators,and was able to significantly enhance the sensitivity of NCI-H460 cells to the clinic chemotherapeutic drug through inhibiting the DNA repairment and enhanced the DNA damage of cancer cells.
文摘目的 对从混合培养的海洋软珊瑚共附生真菌中获得的结构新颖、活性良好的杂萜类成分进行研究。方法采用大米培养基对2株软珊瑚共附生曲霉属真菌EGF7-0-1和EGF15-0-3进行共培养;根据杂萜类化合物的结构特征,在基于质谱的分子网络(GNPS)和薄层色谱(TLC)的共同指导下,运用多种柱色谱及高效液相色谱(HPLC)等方法对其杂萜类成分进行目标导向分离;通过核磁共振(NMR)、高分辨质谱(HRMS)和旋光(ORD)等技术及物理常数对照等手段对单体化合物进行结构鉴定;采用液相色谱质谱联用(LC-MS^(n))和GNPS技术分析比较获得的杂萜类成分在2株真菌共培养及EGF7-0-1单培养中的含量。结果 从2株海洋真菌Aspergillus sp. EGF7-0-1和EGF15-0-3共培养的大米培养基中共分离得到7个杂萜类化合物,结构分别为terretonin (1)、terretonin A (2)、terretonin D1 (3)、terretonin H (4)、terreustoxin E (5)、aperterpene N (6)和asperterpene J (7)。LC-MSn和GNPS分析结果表明共培养条件下杂萜类化合物更为丰富。结论 化合物1~7均为具6/6/6骈并骨架的3,5-二甲基苔色酸(DMOA)途径衍生而成的杂萜。与菌株EGF7-0-1单培养相比,2株真菌共培养可以诱导产生丰富的杂萜,为进一步新颖杂萜类化合物的挖掘提供支持数据。
