Mode of Action of Epoxyphomalins A and B and Characterization of Related Metabolites from the Marine-Derived Fungus Paraconiothyrium sp.

详细信息    查看全文

• 作者：Ietidal E. Mohamed ; Stefan Kehraus ; Anja Krick ; Gabriele M. Knig ; Gerhard Kelter ; Armin Maier ; Heinz-Herbert Fiebig ; Markus Kalesse ; Nisar P. Malek ; Harald Gross
• 刊名：Journal of Natural Products
• 出版年：2010
• 出版时间：December 27, 2010
• 年：2010
• 卷：73
• 期：12
• 页码：2053-2056
• 全文大小：142K
• 年卷期：v.73,no.12(December 27, 2010)
• ISSN：1520-6025

文摘

Epoxyphomalins A (1) and B (2) are highly potent cytotoxic fungal metabolites. During the course of purifying larger quantities of 1 and 2 from Paraconiothyrium sp. fermentation extracts, three new epoxyphomalins (3−5) were isolated and characterized, showing modifications to the oxidation pattern of the cyclohexene moiety or of C-9 of the decalin system. IC₅₀ values for cytotoxicity against a panel of 36 human tumor cell lines were determined for all new compounds. Compound 4 was found to be cytotoxic particularly toward prostate PC3M (IC₅₀ = 0.72 μM) and bladder BXF 1218 L (IC₅₀ = 1.43 μM) cancer cell lines. In addition, inhibition of chymotrypsin-, caspase-, and trypsin-like activity of purified 20S proteasomes was determined for epoxyphomalins A (1) and B (2). The results indicate that compounds 1 and 2 exert their cytotoxic effect through potent inhibition of the 20S proteasome.