异戊二烯化吲哚生物碱主要由曲霉属和青霉属产生，是一类结构有趣的特殊代谢物，具有显着的生物医学意义。在这项研究中，化学引导下分离烟草衍生的内生真菌日本曲霉 TE-739D，产生了八种结构不同的异戊二烯化吲哚生物碱，包括一种未描述的化合物，即 aspertaichamide B (ATB, 1)，以及七种先前发现的衍生物（化合物2 - 8)。它们的化学结构和立体化学特征通过综合光谱分析确定，包括 HRESIMS、NMR、带有 DP4  概率分析的 NMR 计算，以及实验 ECD 数据与基于 DFT 的量子化学计算的比较。对胃癌 MFC 细胞的体外细胞毒作用表明，新化合物 ATB 表现出相当大的活​​性。进一步研究发现ATB抑制MFC细胞的活力、集落形成和迁移能力，并以浓度依赖性方式诱导MFC细胞凋亡。此外，ATB 刺激 MFC 细胞中 ROS 的产生，并抑制 MFC 来源的皮下肿瘤模型中的肿瘤生长，同时不会显着减轻小鼠的体重。药理学结果表明新发现的ATB可能是一种有前途的抗肿瘤先导化合物。要点： • 从真菌 Aspergillus japonicus TE-739D 中分离出八种结构不同的异戊二烯化吲哚生物碱，包括新的天冬酰胺 B (ATB)。 • ATB 的结构通过 HRESIMS、NMR、带有 DP4  概率分析的 NMR 计算和 ECD 计算来阐明。 • ATB 抑制胃癌细胞增殖、促进细胞凋亡、增加 ROS 产生，并对体内肿瘤生长表现出抑制作用。© 2024。作者。

Prenylated indole alkaloids, which are mainly produced by genera Aspergillus and Penicillium, are a class of structurally intriguing specialized metabolites with remarkable biomedical interests. In this study, chemically guided isolation of the Nicotiana tabacum-derived endophytic fungus Aspergillus japonicus TE-739D yielded eight structurally diverse prenylated indole alkaloids, including an undescribed compound, namely aspertaichamide B (ATB, 1), together with seven previously discovered derivatives (compounds 2 - 8). Their chemical structures as well as the stereochemical features were determined by integrated spectroscopic analyses, including HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and a comparison of the experimental ECD data with computed DFT-based quantum chemical calculations. In vitro cytotoxic effects against the gastric cancer MFC cells revealed that the new compound ATB demonstrated considerable activity. Further studies found that ATB suppressed the viability, colony formation, and migration ability of MFC cells, and induced MFC cells apoptosis in a concentration-dependent way. Moreover, ATB stimulated ROS production in MFC cells and inhibited the tumor growth in the MFC-sourced subcutaneous tumor model while not significantly reducing the weight of mice. The pharmacological results suggested that the newly discovered ATB may be a promising anti-tumor lead compound. KEY POINTS: • Eight structurally diverse prenylated indole alkaloids including a new aspertaichamide B (ATB) were isolated from the fungus Aspergillus japonicus TE-739D. • The structure of ATB was elucidated by HRESIMS, NMR, NMR calculations with DP4 + probability analysis, and ECD calculations. • ATB inhibited cell proliferation, promoted apoptosis, and increased ROS production in gastric cancer cells, and exhibited inhibitory effects on tumor growth in vivo.© 2024. The Author(s).