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Cytotoxic Nitrogenated Azaphilones from the Deep-Sea-Derived Fungus Chaetomium globosum MP4-S01-7.
Journal of Natural Products ( IF 5.1 ) Pub Date : 2020-03-20 , DOI: 10.1021/acs.jnatprod.9b01165
Weiyi Wang 1 , Jing Yang 2 , Yan-Yan Liao 3 , Gang Cheng 2 , Jing Chen 2 , Xiang-Dong Cheng 4 , Jiang-Jiang Qin 2, 4 , Zongze Shao 1
Affiliation  

Eight new nitrogenated azaphilones (1-8) and two known compounds (chaetoviridin A and chaetoviridin E, 9, 10) were isolated from the culture of the deep-sea-derived fungus Chaetomium globosum MP4-S01-7. The absolute configurations of new compounds were elucidated by HSQC-HECADE NMR data, J-based configuration analysis, and modified Mosher's method and finally verified by comparison of recorded and computed NMR chemical shifts from quantum chemical calculations coupled with a statistical procedure (DP4+). All of the compounds were evaluated for their in vitro cytotoxicities against the gastric cancer cell lines MGC803 and AGS, and most of them showed significant inhibition on cancer cell viability at 10 μM. Among them, compounds 1, 2, and 5 exerted the most potent cytotoxic activities, with IC50 values less than 1 μM. Further studies showed that compound 2 inhibited cell cycle progression, and both compounds 1 and 2 induced apoptosis of gastric cancer cells in a concentration-dependent manner.

中文翻译:

来自深海真菌球ChaMP4-S01-7的细胞毒性氮杂氮酮。

从深海来源的真菌球壳龟(Chaetomium globosum)MP4-S01-7的培养物中分离出八种新的硝化氮杂苯甲酮(1-8)和两种已知化合物(chaetoviridin A和chaetoviridin E,9、10)。通过HSQC-HECADE NMR数据,J型构型分析和改进的Mosher方法阐明了新化合物的绝对构型,最后通过比较记录的和计算的NMR化学位移(通过量子化学计算结合统计程序(DP4 +))进行了验证。评估了所有化合物对胃癌细胞系MGC803和AGS的体外细胞毒性,其中大多数在10μM时均表现出对癌细胞生存能力的显着抑制作用。其中,化合物1、2和5具有最强的细胞毒活性,IC50值小于1μM。
更新日期:2020-03-20
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