The limitations of currently available antifungal agents and the rapid emergence of drug-resistant strains necessitate more efficient approaches to screening and developing novel antifungal drugs. The antifungal activity of the natural products of a series of plants was evaluated and wighteone, 5, 7, 4'-trihydroxy-6-(gamma,gamma-dimethylallyl)isoflavone showed excellent anti-yeast activity (MIC against Saccharomyces cerevisiae was 4 microg/ml). Transcriptome profiling of wighteone-treated S. cerevisiae indicated that wighteone is different from commonly used antifungal compounds in its mode of action.