Design, Synthesis, and Biological Evaluation of Novel Matrine Oxime Ester Derivatives

Plant pathogenic fungi are seriously threatening agricultural production. There is an urgent need to develop novel fungicides with low toxicity and high efficiency. In this study, we synthesized 26 oxime ester derivatives of matrine and systematically evaluated their antifungicidal activities toward seven common phytopathogenic fungi. The <i>in vitro</i> assay against <i>Sclerotinia sclerotiorum</i> (<i>S. sclerotiorum</i>) showed that the EC₅₀ value of compound <b>5-11</b> (EC₅₀: 7.2 μg/mL) is almost 4 times lower than that of azoxystrobin (EC₅₀: 28.3 μg/mL). Preliminary fungicidal research indicated that compound <b>5-11</b> has a certain destructive effect on the hyphae of <i>S. sclerotiorum</i>. Furthermore, molecular docking and molecular dynamics simulation analysis demonstrated that the potent insecticidal activity of <b>5-11</b> is likely mediated by its specific interactions with SDH primarily through the π-cation interaction and the hydrophobic interactions with key residues. This work lays a foundation for the application of matrix derivatives in plant protection.