Cytotoxic Nitrogenated Azaphilones from the Deep-Sea-Derived Fungus Chaetomium globosum MP4-S01-7
- 20 March 2020
- journal article
- research article
- Published by American Chemical Society (ACS) in Journal of Natural Products
- Vol. 83 (4), 1157-1166
- https://doi.org/10.1021/acs.jnatprod.9b01165
Abstract
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 invitro 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.Keywords
Funding Information
- Natural Science Foundation of Fujian Province (2018J01064)
- National Natural Science Foundation of China (81573953, 81903842)
- Foundation of Third Institute of Oceanography SOA (2017001, 2018021)
- Medical Science and Technology Project of Zhejiang Province (WKJ-ZJ-1728)
- Zhejiang Provincial Science and Technology Projects (2019C03049)
- COMRA Program (DY135-B2-01, DY135-B2-05)
- Zhejiang Chinese Medical University Startup Funding (11110000000000000000)
- Program of zhejiang provincial tcm sci-tech plan (2016ZZ012, 2020ZZ005)
- Traditional Chinese Medical Science and Technology Major Project of Zhejiang Province (2018ZY006)
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