Chen Min, Hao Bao-Cong, Zhu Xia-Hao, Zhang Li-Kui, Zheng Yao-Yao, Zhou Xiao-Jian, Schäberle Till F, Shen Li, Wang Chang-Yun, Liu Yang
Marine Science & Technology Institute, College of Environmental Science & Engineering, Yangzhou University, 196#, Huayang West Street, Yangzhou, 225127 China.
Key Laboratory of Marine Drugs, The Ministry of Education of China, Institute of Evolution & Marine Biodiversity, School of Medicine and Pharmacy, Ocean University of China, Qingdao, 266003 China.
Mar Life Sci Technol. 2025 Apr 7;7(2):302-312. doi: 10.1007/s42995-024-00274-6. eCollection 2025 May.
MS/MS-based molecular networking is an effective strategy to rapidly dereplicate known compounds and to guide the discovery process for new and novel natural products. In the present study, the chemical diversity of indole diterpenoids from the marine-derived fungus sp. N4-3 was investigated using molecular networking techniques. Guided by this information, targeted isolation resulted in two new indole diterpenoids shearinines R and S (, ) and an oxidative artifact shearinine T (), together with the verification of two known analogs (, ). Furthermore, five indole diterpenoids (-), including three putatively new ones, shearinines U-W (, , ), were predicted from the molecular ion cluster by the combination of GNPS molecular networking and manual analysis of MS/MS fragmentation clusters. Shearinines T () and W () are characterized by an oxidative cleavage of the C-2-C-18 double bond. Feature fragment ions of these shearinines revealed two type of dominant ions related to the indole moiety and the breaking of C-9 side chain or Ring I. Compound showed antibacterial activities against a panel of pathogenic bacteria with IC values ranging from 6.34 to 47.96 μg/mL and inhibited the growth of the human hepatic (HepG2) and gastric (SGC-7901) cancer cells lines with IC values of 6.27 and 19.16 μg/mL, respectively.
The online version contains supplementary material available at 10.1007/s42995-024-00274-6.
基于串联质谱的分子网络是一种快速去除已知化合物冗余并指导新天然产物发现过程的有效策略。在本研究中,使用分子网络技术研究了海洋来源真菌sp. N4-3中吲哚二萜类化合物的化学多样性。在此信息的指导下,通过靶向分离得到了两种新的吲哚二萜类化合物shearinines R和S(,)以及一种氧化产物shearinine T(),同时还验证了两种已知类似物(,)。此外,通过全球天然产物社会分子网络(GNPS)分子网络与串联质谱碎片簇的手动分析相结合,从分子离子簇中预测出了五种吲哚二萜类化合物(-),其中包括三种可能的新化合物shearinines U-W(,,)。Shearinines T()和W()的特征是C-2-C-18双键发生氧化裂解。这些shearinines的特征碎片离子揭示了与吲哚部分以及C-9侧链或环I断裂相关的两种主要离子类型。化合物对一组病原菌具有抗菌活性,IC值范围为6.34至47.96μg/mL,对人肝癌(HepG2)和胃癌(SGC-7901)细胞系的生长具有抑制作用,IC值分别为6.27和19.16μg/mL。
在线版本包含可在10.1007/s42995-024-00274-6获取的补充材料。