Characterization of the mechanism of action of the fungicide fenpicoxamid and its metabolite UK‐2A

BACKGROUND

Fenpicoxamid is a new fungicide for control of Zymoseptoria tritici, and is a derivative of the natural product UK‐2A. Its mode of action and target site interactions have been investigated.

RESULTS

UK‐2A strongly inhibited cytochrome c reductase, whereas fenpicoxamid was much less active, consistent with UK‐2A being the fungicidally active species generated from fenpicoxamid by metabolism. Both compounds caused rapid loss of mitochondrial membrane potential in Z. tritici spores. In Saccharomyces cerevisiae, amino acid substitutions N31K, G37C and L198F at the Qi quinone binding site of cytochrome b reduced sensitivity to fenpicoxamid, UK‐2A and antimycin A. Activity of fenpicoxamid was not reduced by the G143A exchange responsible for strobilurin resistance. A docking pose for UK‐2A at the Qi site overlaid that of antimycin A. Activity towards Botrytis cinerea was potentiated by salicylhydroxamic acid, showing an ability of alternative respiration to mitigate activity. Fungitoxicity assays against Z. tritici field isolates showed no cross‐resistance to strobilurin, azole or benzimidazole fungicides.

CONCLUSION

Fenpicoxamid is a Qi inhibitor fungicide that provides a new mode of action for Z. tritici control. Mutational and modeling studies suggest that the active species UK‐2A binds at the Qi site in a similar, but not identical, fashion to antimycin A. © 2017 The Authors. Pest Management Science published by John Wiley & Sons Ltd on behalf of Society of Chemical Industry.     

Synthesis and antifungal activity of 2‐azetidinonyl‐5‐(2‐benzoylphenoxy)methyl‐1,3,4‐oxadiazoles against seed‐borne pathogens of Eleusine coracana (L.) Gaertn

BACKGROUND: Finger millet is a major food crop as well as feed and fodder for livestock, especially in regions of southern India. A sturdy crop to fluctuating environmental conditions, it can be cultivated in all seasons of the year. Leaf, neck and finger blast caused by Pyricularia grisea Sacc. and Bipolaris setariae (Saw.) Shoem, as well as leaf spot disease, Bipolaris nodulosa (Berk & M.A.Curtis) Shoem, are major production constraints in southern India. Apart from environmental conditions, the use of harvested seeds by farmers is a major reason for disease prevalence. Benzophenone analogues have been investigated for controlling phytopathogenic fungi. In addition, the most important applications of azetidin‐2‐ones are as antibiotics. Based on this information, the present study was conducted to explore the antifungal activity of integrated 2‐azetidinonyl and 1,3,4‐oxadiazoles moieties into a benzophenone framework. RESULTS: A simple high‐yielding method for the integration of heterocyclic rings, namely 2‐azetidinonyl, at the benzophenone nucleus has been achieved, starting from substituted 2‐hydroxybenzophenones under mild conditions on a wet solid surface using microwave irradiation. In the present study, an array of newly synthesised compounds, 2‐azetidinonyl‐5‐(2‐benzoylphenoxy)methyl‐1,3,4‐oxadiazoles, were screened for their antifungal property against blast and leaf spot causing fungi associated with the seeds of finger millet, cv. Indof‐9. CONCLUSION: Two of the newly synthesised compounds showed promising effects in depleting the incidence of seed‐borne pathogenic fungi of finger millet. The suppression of Pyricularia grisea and Bipolaris setariae resulted in enhanced seed germination and seedling growth. Copyright © 2009 Society of Chemical Industry