海洋真菌Talaromyces sp.HK1-18的嗜氮酮类化合物化学多样性研究

Chemical diversity of azaphilones from the marine-derived fungus Talaromyces sp.HK1-18

基于GNPS的质谱-分子网络策略是快速识别已知天然产物和发现新颖化合物的有效方法。本文利用分子网络技术研究了海洋真菌Talaromyces sp.HK1-18发酵产物中的嗜氮酮类化合物的化学多样性。综合采用硅胶柱色谱和高效液相色谱等色谱分离技术以及核磁共振和高分辨质谱等波谱解析技术从真菌HK1-18发酵产物中分离并鉴定了3个线型三环嗜氮酮化合物sequoiamonacins A~C (2a、2b、1);继而以其质谱为指导,从该真菌的全分子网络中提取了sequoiamonacin类嗜氮酮化合物的分子聚簇;通过解析该聚簇中各母离子的MS/MS (二级质谱)碎片,成功预测了7个嗜氮酮化合物的化学结构(3~9),其中sequoiamonacins E~J (4~9)为新化合物,并揭示了该类化合物的MS/MS裂解规律。化合物1具有一定的抗炎活性,其能抑制脂多糖(LPS)诱导的小鼠巨噬细胞RAW264.7中白细胞介素1α (IL-1α)的产生,质量浓度为12.5μg·mL^(-1)时,抑制率达29%。

GNPS-based mass spectrum-molecular networks is an effective strategy for rapidly identifying known natural products and discovering novel structures.The chemical diversity of azaphilones from the fermentation extracts of Talaromyces sp.HK1-18 was studied by molecular network technique.Three linear tricyclic azaphilones,sequoiamonacins A-C(2a,2b,1),were isolated by silica gel column chromatography and high performance liquid chromatography from the extracts of the fungal strain of HK1-18,and their structures were identified by nuclear magnetic resonance and high-resolution mass spectrometry.Guided by the mass spectra of sequoiamonacins A-C(2a,2b,1),the cluster of sequoiamonacinoid analogues was discovered from the full molecular networking of HK1-18.By analyzing the MS/MS fragments of each parent ion in this cluster,7azaphilones(3-9) included 6 new ones(4-9) were predicted successfully.Then the MS/MS cracking regularity of this type of azaphilones was revealed.Compound 1 showed anti-inflammatory activity,which can inhibit the production of interleukin-1α(IL-1α) in lipopolysaccharide(LPS)-induced mouse macrophage RAW264.7,with an inhibitory rate of 29% at the concentration of 12.5 μg·mL~(-1).