Trifluoromethyloxadiazoles – Inhibitors of histone deacetylases for control of Asian Soybean Rust.
Pest Manag Sci. 2020 May 05;:
Authors: Winter C, Fehr M, Craig IR, Grammenos W, Wiebe C, Terteryan-Seiser V, Rudolf G, Mentzel T, Quintero Palomar MA
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 only showed activity against 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 histone deacetylases of Aspergillus nidulans. Studies of the enzyme-inhibitor binding mode using protein structural information based on the crystal structure of human HDAC4 argue that the TFMOs only inhibit these enzymes 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 HDACs fungicides would offer the potential to control fungal isolates that show reduced sensitivity towards existing commercial fungicides. This article is protected by copyright. All rights reserved.
PMID: 32369266 [PubMed – as supplied by publisher]