College of Pharmacy and Research Institute of Life and Pharmaceutical Sciences, Sunchon National University, Sunchon 57922, Republic of Korea.
Department of Chemistry and Nanoscience, Ewha Womans University, Seoul 03760, Republic of Korea.
Mar Drugs. 2023 Feb 25;21(3):153. doi: 10.3390/md21030153.
Marinobazzanan (), a new bazzanane-type sesquiterpenoid, was isolated from a marine-derived fungus belonging to the genus . The chemical structure of was elucidated using NMR and mass spectroscopic data, while the relative configurations were established through the analysis of NOESY data. The absolute configurations of were determined by the modified Mosher's method as well as vibrational circular dichroism (VCD) spectra calculation and it was determined as 6, 7, 9, and 10. It was found that compound was not cytotoxic to human cancer cells, including A549 (lung cancer), AGS (gastric cancer), and Caco-2 (colorectal cancer) below the concentration of 25 μM. However, compound was shown to significantly decrease cancer-cell migration and invasion and soft-agar colony-formation ability at concentrations ranging from 1 to 5 μM by downregulating the expression level of KITENIN and upregulating the expression level of KAI1. Compound suppressed β-catenin-mediated TOPFLASH activity and its downstream targets in AGS, A549, and Caco-2 and slightly suppressed the Notch signal pathway in three cancer cells. Furthermore, also reduced the number of metastatic nodules in an intraperitoneal xenograft mouse model.
马林巴扎南（），一种新型的倍半萜，从属于 的海洋来源真菌中分离得到。通过 NMR 和质谱数据阐明了 的化学结构，而通过 NOESY 数据分析确定了相对构型。通过改进的 Mosher 方法以及振动圆二色性（VCD）光谱计算确定了 的绝对构型，确定为 6,7,9 和 10。结果表明，化合物 在低于 25 μM 的浓度下对人癌细胞（肺癌 A549、胃癌 AGS 和结直肠癌 Caco-2）没有细胞毒性。然而，化合物 在 1 至 5 μM 的浓度范围内通过下调 KITENIN 的表达水平和上调 KAI1 的表达水平，显著降低了癌细胞的迁移和侵袭以及软琼脂集落形成能力。化合物 抑制了 AGS、A549 和 Caco-2 中 β-catenin 介导的 TOPFLASH 活性及其下游靶标，并且在三种癌细胞中轻微抑制了 Notch 信号通路。此外， 还减少了腹腔异种移植小鼠模型中的转移结节数量。
