To date, entomopathogenic fungi have not been extensively examined by natural product chemists. In this study, we isolated novel pyrone diterpene-type compounds, metarhizins A (1) and B (2), from methanol extracts of entomopathogenic fungus, Metarhizium flavoviride. They showed potent and selective antiproliferative activity against both insect and human cancer cell lines. These results indicate that metarhizins A (1) and B (2) can be used as novel lead compounds for anti-cancer agents and probes for cell cycle regulation. To further investigate the structural requirements for this inhibitory activity, we synthesized many metarhizin derivatives and evaluated their antiproliferative activities.
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