Novel flavonoid derivatives containing 1,2,4-triazolo[4,3-a]pyridine as potential antifungal agents: Design, synthesis, and biological evaluation

A series of flavonoid derivatives containing 1,2,4-triazolo[4,3-a]pyridine were designed, synthesized and evaluated for their antifungal activity. Bioactivity tests showed that some target compounds exhibited the strong antifungal activity against Botrytis cinerea (B. cinerea), Sclerotinia sclerotiorum (S. sclerotiorum), and Phomopsis sp. Among them, the half maximal effective concentration (EC50) value of S2 against B. cinerea was 3.3 μg/mL, which was less than that of the control drug azoxystrobin (21.0 μg/mL). The EC50 value of S2 against S. sclerotiorum was 12.7 μg/mL, which was better than that of azoxystrobin (28.1 μg/mL). In addition, the in vivo protective and curative activities of S2 against blueberry were 92.0 and 79.8 % at 200 μg/mL, respectively, which were higher than those of the control drug azoxystrobin (89.4 and 71.7%). Scanning electron microscopy (SEM) and spore germination experiments showed that S2 could not only cause the mycelium damage but also inhibited the spore germination. Fluorescence microscopy (FM) observation, relative electrical conductivity measurement and cytoplasmic leakage assays indicated that S2 could affect cell membrane integrity by inducing lipid peroxidation and increasing cell membrane permeability as well as causing leakage of cytoplasmic contents. These results show that flavonoid derivatives containing 1,2,4-triazolo[4,3-a]pyridine had excellent inhibitory effects on B. cinerea, providing another supplement for the development of new pesticides.