Bioactive molecular family construction: Design, optimization and antifungal mechanism study of novel 2-phenylglycine derivatives

With the widespread use of fungicides, some problems have also gradually emerged, such as resistance, toxicity and residues. Therefore, to develop novel antifungal pesticides with unique structures, safety and high efficiency, a series of 2-phenylglycine derivatives were designed and synthesized. The bioactivity results revealed good antifungal activity of compound III11 and boscalid against Nigrospora oryzae, and they both effectively inhibited spore germination with EC50 values of 17.3 and 3.1 μg/mL, respectively. An antifungal mechanism study showed that both III11 and boscalid significantly increased the content of nucleic acids, proteins and MDA, which indicated that they could destroy the integrity of the mycelial cell membrane, thus affecting the normal growth of mycelia. Molecular docking results revealed that III11 bound with some amino acid residues (SER-39, ARG-14 and ARG-43) of succinate dehydrogenase (SDH) through a unique mode involving hydrogen bonds, different from the binding mode of boscalid. Further investigation demonstrated that III11 exhibited moderate inhibitory activity against SDH (IC50 = 54.5 μg/mL), weaker than that of boscalid (IC50 = 10.7 μg/mL). The results provided sufficient support for the optimization and derivatization of 2-phenylglycine derivatives, which could be further developed and designed as potential fungicides.