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Novel drimane-type sesquiterpenoids and nucleosides from the Helicoma septoconstrictum suppress the growth of ovarian cancer cells
Bioorganic Chemistry ( IF 5.1 ) Pub Date : 2024-02-23 , DOI: 10.1016/j.bioorg.2024.107214
Wen Zheng , Long Han , Zhang-Jiang He , Ji-Chuan Kang

Four new drimane-type sesquiterpenoids and two new nucleoside derivatives (1–6), were isolated from the fungus Their structures were determined based on the combination of the analysis of their HR-ESI-MS, NMR, ECD calculations data and acid hydrolysis. All the isolated compounds were detected for their bio-activities against MDA-MB-231, A549/DDP, A2780 and HepG2 cell lines. Helicoside C (4) exhibited superior cytotoxicity against the A2780 cell line with IC 7.5 ± 1.5 µM. The analysis of reactive oxygen species (ROS) revealed that Helicoside C induced an increase in intracellular ROS. Furthermore, the flow cytometry and mitochondrial membrane potential (MMP) analyses unveiled that Helicoside C mediated mitochondrial-dependent apoptosis in A2780 cells. The western blotting test showed that Helicoside C could suppress the STAT3′s phosphorylation. These findings offered crucial support for development of and highlighted the potential application of drimane-type sesquiterpenoids in pharmaceuticals.

中文翻译:

来自 Helicoma septoconstrictum 的新型 Drimane 型倍半萜类化合物和核苷可抑制卵巢癌细胞的生长

从真菌中分离出四种新的杜马烷型倍半萜类化合物和两种新的核苷衍生物(1-6),结合HR-ESI-MS、NMR、ECD计算数据和酸水解分析,确定了它们的结构。检测了所有分离的化合物对 MDA-MB-231、A549/DDP、A2780 和 HepG2 细胞系的生物活性。 Helicoside C (4) 对 A2780 细胞系表现出优异的细胞毒性,IC 为 7.5 ± 1.5 µM。活性氧 (ROS) 分析表明螺旋苷 C 诱导细胞内 ROS 增加。此外,流式细胞术和线粒体膜电位 (MMP) 分析揭示螺旋苷 C 介导 A2780 细胞中线粒体依赖性细胞凋亡。 Western blotting测试表明Helicoside C可以抑制STAT3的磷酸化。这些发现为二马烷型倍半萜类化合物的开发提供了重要支持,并强调了其在药物中的潜在应用。
更新日期:2024-02-23
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