Non-food bioactive products: Diversified invention of 1,2,4-oxadiazole-containing amide derivatives for novel fungicidal candidate discovery

In an effort for novel fungicidal candidate discovery, a series of diversified 1,2,4-oxadiazole-containing amide derivatives were devised and synthesized. Through an extensive screening of fungicidal activity on four common phytopathogens, all the target compounds exerted satisfactory inhibitory effect on Valsa mali . A detailed and specific discussion on structure and activity relationship (SAR) indicated that the tetrahydro(iso)quinoline substitution was crucial for activity improvement. The EC 50 values of compounds 6i , 6p , 6u , 6v , and 6z were far more prominent than the commercial fungicide boscalid. The biochemistry and physiology response of V. mali after treatment with the remarkable compound 6p was examined, and the fruit body production, hyphae morphology, cell membrane permeability , cell wall integrity, and pectinase activity were profoundly affected. In addition, two representative compounds 6p and 6t were picked out for theoretical calculation to assess the most paramount molecular descriptors. The highest and lowest unoccupied molecular orbital (LUMO, HOMO), molecular electrostatic potential (MEP) and electron density (ED) map of compounds were obtained, plotted, and visualized. Based on the integrated analysis of fungicidal activity, biochemistry and physiology response and theoretical calculation, this work would provide some insight for novel fungicide invention and potential mode of action study. • Structurally diverse and versatile oxadiazole-containing amides were devised. • A systematic study of activity, mode of action and calculation was carried out. • Compound 6p exhibited outstanding antifungal activity against Valsa mali .