Eurochevalierines A – I, Sesquiterpene Alkaloid Hybrids with Anti-Triple Negative Breast Cancer Activity from Penicillium sp. HZ-5

作者：Yeting Zhang, Yeting Zhang, Qiang Li, Jinlong Zhang, Ming Chen, Xuan Li, Yuben Qiao, Kuansong Wang, Changxing Qi, Yonghui Zhang, Yonghui Zhang · 发表于：Journal of Agricultural and Food Chemistry · 年份：2024 · DOI：10.1021/acs.jafc.4c04011 · 被引用次数：12 · 研究领域：Microbial Natural Products and Biosynthesis、Cancer Treatment and Pharmacology、Fungal Biology and Applications

Nine new sesquiterpene alkaloids, eurochevalierines A – I ( 1 – 9 ), were separated from the rice cultures of the endophytic fungus Penicillium sp. HZ-5 originated from the fresh leaf of Hypericum wilsonii N. Robson. The structures’ illumination was conducted by single-crystal X-ray diffraction, extensive spectroscopic analysis, alkaline hydrolysis reaction, and Snatzke’s method. Importantly, the antitumor activities screen of these isolates indicated that 1 could suppress triple negative breast cancer (TNBC) cell proliferation and induce apoptosis, with an IC 50 value of 5.4 μ M, which is comparable to the positive control docetaxel (DXT). Flow cytometry experiments mentioned that compound 1 significantly reduced mitochondrial membrane potential (MMP) of TNBC cells. In addition, 1 could activate caspase-3 and elevated the levels of reactive oxygen species (ROS) and expressions of suppressive cytokines and chemokines. Further Western blot analysis showed that 1 could selectively induce mitochondria-dependent apoptosis in TNBC cells via the BAX/BCL-2 pathway. Remarkably, these finding provide a new natural product skeleton for the treatment of TNBC.