期刊
JOURNAL OF NATURAL PRODUCTS
卷 85, 期 4, 页码 1067-1078出版社
AMER CHEMICAL SOC
DOI: 10.1021/acs.jnatprod.1c01194
关键词
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资金
- COMRA [DY135-B-05]
- NSFC [81991525, 21861142006, 81872793, 81630089]
- BJFC [7202090, 2021Z046]
Bioassay-guided fractionation, combined with LC-MS and NMR detection, led to the discovery of six new alkaloids from a marine gorgonian-derived fungus. Among them, sclerotiamides C and F showed significant inhibition against tumor cell lines, and sclerotiamide C induced apoptosis in cervical cancer cells.
Bioassay-guided fractionation in association with LC-MS and NMR detection led to the isolation of six new alkaloids, sclerotiamides C-H (1-6), from the marine gorgonian-derived fungus Aspergillus sclerotiorum LZDX-33-4. Their structures were determined from extensive spectroscopic data, including ECD data and single-crystal X-ray diffraction analysis for configurational assignments. Sclerotiamides C (1) and D (2) are notoamide-type alkaloids with the incorporation of a unique 2,2-diaminopropane unit, and sclerotiamides E (3) and F (4) are unprecedented notoamide hybrids with a new coumarin unit. Sclerotiamide H (6) represents a new highly oxidized notoamide scaffold. Sclerotiamides C and F showed significant inhibition against a panel of tumor cell lines with IC50 values ranging from 1.6 to 7.9 mu M. Sclerotiamide C induces apoptosis in HeLa cells by arresting the cell cycle, activating ROS production, and regulating apoptosis-related proteins in the MAPK signaling pathway. The present study extends the scaffold diversity of the notoamides and provides a potential lead for the development of a cytotoxic agent.
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