Trifluoromethyloxadiazoles: inhibitors of histone deacetylases for control of Asian soybean rust.

Background: Trifluoromethyloxadiazoles (TFMOs) are selective inhibitors of class II histone deacetylases (HDACs). To date, class II HDACs have not been addressed as target enzymes by commercial fungicides.

Results: Antifungal testing of a broad variety of TFMOs against several important plant pathogens showed activity against only rusts, and especially Phakopsora pachyrhizi, the cause of Asian soybean rust. A structure-activity relationship was established, leading to highly active fungicides that inhibit fungal class II and HOS3-type HDACs of Aspergillus nidulans. Studies of the enzyme-inhibitor binding mode using protein structural information based on the crystal structure of human HDAC4 argue that TFMOs inhibit these enzymes only after undergoing hydration.

Conclusion: Fungal class II HDACs are potential target enzymes for the control of at least some biotrophic crop diseases, in particular Asian soybean rust. As with any novel mode-of-action, class II HDAC fungicides would offer the potential to control fungal isolates that show reduced sensitivity toward existing commercial fungicides.