Dai Xiaojun, Xia Zixuan, Lai Changrong, Li Xunuo, Tu Jieyuan, Tian Danmei, Wu Bin, Tang Jinshan
Institute of Traditional Chinese Medicine and Natural Products, College of Pharmacy/State Key Laboratory of Bioactive Molecules and Druggability Assessment/International Cooperative Laboratory of Traditional Chinese Medicine Modernization and Innovative Drug Development of Ministry of Education (MOE) of China, Jinan University, Guangzhou 510632, China.
School of Traditional Chinese Materia Medica, Shenyang Pharmaceutical University, Shenyang 110016, Liaoning, China.
Fitoterapia. 2025 Sep;185:106733. doi: 10.1016/j.fitote.2025.106733. Epub 2025 Jul 14.
This study described the isolation and structural characterization of four novel linearly fused prenylated indole diketopiperazine alkaloids (1-4) alongside four known analogues from the marine-derived fungus Aspergillus sp. MG35-18, guided by LC-MS/MS-based molecular networking. These compounds are characterized with a rare [3,2-f] indole-pyrano fused ring system. Structural elucidation was achieved through HR-ESI-MS and comprehensive 1D and 2D NMR analyses, including H, C, HH COSY, HSQC, and HMBC spectroscopy. Furthermore, the stereochemistry of new compounds 1-4 was determined via NOESY correlations, electronic circular dichroism (ECD) calculation, Marfey's method and comparison with literature data. Subsequent anti-inflammatory activity assessments revealed that compounds 4-8, particularly 6, exhibited significant inhibitory effects on lipopolysaccharide (LPS)-induced nitric oxide (NO) overproduction in murine macrophage RAW264.7 cells at 20 μM. Moreover, no cytotoxicity was observed at the tested concentration. Notably, compound 6 demonstrated potent inhibitory effects on LPS stimulated release of NO, interleukin-6 (IL-6), and tumor necrosis factor-alpha (TNF-α) in a dose-dependent manner, suggesting its promising anti-inflammatory potential.
本研究描述了基于液相色谱-串联质谱（LC-MS/MS）的分子网络指导下，从海洋来源的曲霉属真菌Aspergillus sp. MG35-18中分离得到的四种新型线性稠合的异戊烯基化吲哚二酮哌嗪生物碱（1-4）以及四种已知类似物，并对其进行了结构表征。这些化合物的特征是具有罕见的[3,2-f]吲哚-吡喃稠合环系统。通过高分辨电喷雾电离质谱（HR-ESI-MS）以及全面的一维和二维核磁共振（NMR）分析，包括氢谱、碳谱、氢-氢化学位移相关谱（HH COSY）、异核单量子相干谱（HSQC）和异核多键相关谱（HMBC），实现了结构解析。此外，通过核Overhauser效应光谱（NOESY）相关、电子圆二色光谱（ECD）计算、马尔费伊法以及与文献数据比较，确定了新化合物1-4的立体化学。随后的抗炎活性评估表明，化合物4-8，尤其是化合物6，在20 μM浓度下对脂多糖（LPS）诱导的小鼠巨噬细胞RAW264.7细胞中一氧化氮（NO）过量产生具有显著抑制作用。此外，在测试浓度下未观察到细胞毒性。值得注意的是，化合物6对LPS刺激的NO、白细胞介素-6（IL-6）和肿瘤坏死因子-α（TNF-α）释放具有剂量依赖性的强效抑制作用，表明其具有良好的抗炎潜力。
