551. Genkwalathins A and B, new lathyrane-type diterpenes from Daphne genkwa.
- Author
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Van Minh N, Han BS, Choi HY, Byun J, Park JS, and Kim WG
- Subjects
- Animals, Anti-Inflammatory Agents, Non-Steroidal chemistry, Anti-Inflammatory Agents, Non-Steroidal pharmacology, Cell Line, Cell Survival drug effects, Diterpenes chemistry, Drug Evaluation, Preclinical, Lipopolysaccharides pharmacology, Magnetic Resonance Spectroscopy, Mice, Microglia cytology, Molecular Structure, Nitric Oxide metabolism, Structure-Activity Relationship, Thymelaeaceae chemistry, Daphne chemistry, Diterpenes pharmacology
- Abstract
Screening for new natural anti-neuroinflammatory compounds was performed with the traditional folk medicine Genkwa Flos, which potently inhibited nitric oxide (NO) production by LPS-activated microglial BV-2 cells. Two new lathyrane-type diterpenes, genkwalathins A (1) and B (2), and 14 known daphnane-type diterpenes (3-16) were isolated. The lathyrane-type diterpenes were isolated for the first time from the Thymelaeaceae family in this study. Compounds 1 and 2 moderately inhibited LPS-induced NO production in BV-2 cells without affecting cell viability, while six daphnane-type diterpenes (3, 4, 6, 7, 9 and 10) potently reduced NO production with IC
50 values less than 1 μM, although they did display weak cytotoxicity. A structure-activity relationship study on the daphnane-type diterpenes indicated that the stereochemistry at C-19, the benzoate group at C-20, and the epoxide moiety could be important for their anti-neuroinflammatory effects.- Published
- 2018
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