Undefeated-Changing the phenamacril scaffold is not enough to beat resistant Fusarium.

Filamentous fungi belonging to the genus Fusarium are notorious plant-pathogens that infect, damage and contaminate a wide variety of important crops. Phenamacril is the first member of a novel class of single-site acting cyanoacrylate fungicides which has proven highly effective against important members of the genus Fusarium. However, the recent emergence of field-resistant strains exhibiting qualitative resistance poses a major obstacle for the continued use of phenamacril. In this study, we synthesized novel cyanoacrylate compounds based on the phenamacril-scaffold to test their growth-inhibitory potential against wild-type Fusarium and phenamacril-resistant strains. Our findings show that most chemical modifications to the phenamacril-scaffold are associated with almost complete loss of fungicidal activity and in vitro inhibition of myosin motor domain ATPase activity.

Aerobic dissipation of the novel cyanoacrylate fungicide phenamacril in soil and sludge incubations.

The cyanoacrylate ethyl (2Z)-3-amino-2-cyano-3-phenylacrylate (phenamacril), has been introduced as an effective agent against several fungi species belonging to the Fusarium genus. However, in current literature, knowledge about the environmental behavior of this fungicide is limited and there are no data on the degradation in the environment. By performing tests on inherent degradability as well as degradation studies in soils this study provides the only published information regarding the environmental stability and degradation kinetics of this compound. Tests for inherent/ready biodegradation revealed the phenamacril is inherently degradable with zero order kinetics, even though the degradation is comparatively slow. Degradation of phenamacril in soil was found to occur following first order kinetics with a final plateau with a half live of 17.1 days (i.e. more rapidly than tebuconazole but less rapidly than octylisothiazolinone).

Real-time imaging of the growth-inhibitory effect of JS399-19 on Fusarium.

Real-time imaging was used to study the effects of a novel Fusarium-specific cyanoacrylate fungicide (JS399-19) on growth and morphology of four Fusarium sp. This fungicide targets the motor domain of type I myosin. Fusarium graminearum PH-1, Fusarium solani f. sp. pisi 77-13-4, Fusarium avenaceum IBT8464, and Fusarium avenaceum 05001, which has a K216Q amino-acid substitution at the resistance-implicated site in its myosin type I motor domain, were analyzed. Real-time imaging shows that JS399-19 inhibits fungal growth but not to the extent previously reported. The fungicide causes the hypha to become entangled and unable to extend vertically. This implies that type I myosin in Fusarium is essential for hyphal and mycelia propagation. The K216Q substitution correlates with reduced susceptibility in F. avenaceum.