Design and Discovery of α-Oximido-arylacetamides as Novel Antifungal Leads.

The discovery of novel and easily accessible antifungal compounds is an imperative issue in agrochemical innovation. Our continuing research with the -aminophenyloxazoline () scaffold demonstrated the viability of introducing phenylacetamides for identifying novel antifungal leads. An antifungal function-oriented molecular evaluation was conducted for the previously identified lead . Fine-tuning of the α-position and scaffold hopping of acid segment and enables α-oximido-arylacetamide as a novel antifungal model. The concomitant function-oriented diversification produces a panel of antifungal leads , , and against and . The crucial and multidimensional effect of the configuration of the acquired amides on the antifungal performance is demonstrated specifically by the separable isomers. The -isomer (), with an EC value of 0.97 μM against , is significantly more potent than its -isomer () and the positive control boscalid. More importantly, compound can efficiently inhibit resistant strains. demonstrates a better preventative effect (82.1%) than those of (48.1%) and boscalid (55.1%) at 100 μM. showed a distinct binding model from those of the boscalid and in the molecular docking simulation. A further morphological investigation by scanning electron microscopy revealed the different mycelia shrinkage of treated by isomers. The easy accessibility and cost-effectiveness demonstrated the practical potential of α-oximido-phenylacetamide containing as a new model for agrochemical innovation.