No abstract

Potent and selective myosin inhibitors are of vast scientific interest in the development of treatments for diseases involving myosin dysfunction or overactivity. A novel fungicide, ethyl 2‐cyano‐3‐amino‐3‐phenylacrylate (commercialized as “phenamacril”), was recently identified as an inhibitor of myosin‐5 in F. graminearum. Although the compound has been known since 1900, a general confusion concerning the stereochemical configuration at the exocyclic double bond persists in the literature, thus restricting further drug development of this compound and derivatives. By using NMR and quantum mechanical calculations, this work establishes the stereoconfiguration as the (Z) form and that the effect of a single hydrogen bond is crucial in keeping these types of molecules in a single configuration.

No abstract

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.

No abstract