| Research Abstract |
We have been screening microbial metabolites of soil actinomycetes and fungi to obtain new cell cycle inhibitors. The cell cycle analysis was carried out by flow cytometry using tsFT210 cell, a temperature-sensitive mutant cell line of cdc2 kinase. During this screening, a new cell cycle inhibitor named curvularol was discovered from the fermentation broth of a fungus, Curvularia sp. 97-F166, isolated in Nagasaki Prefecture. Curvularol was purified by a successive column chromatography and obtained as a colorless needle crystal. Its molecular weight and molecular formula were determined to be 266 and C_<15>H_<22>O_4, respectively, according to high-resolution FAB mass spectrometry. The structure of curvularol was elucidated by the detailed analyses of its 1D and 2D NMR spectra. It is a new sesquiterpen structurally related to trichotecenes to some extent.
Curvularol showed a weak antimicrobial activity at the concentration of 100 μg/ml, but showed a strong cytotoxicity at the concentration range of 50〜500 ng/ml, in vitro. The effect of curvularol against the cellular macromolecular synthesis was examined, and the primary target of curvularol was suggested to be protein synthesis. It blocked the cell cycle progression at G1 phase of various cell lines including, tsFT210, src^<ts>-NRK at 50 ng/ml.
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