Plant
diseases caused by phytopathogenic fungi reduce the yield
and quality of crops. To develop novel antifungal agents, we designed
and synthesized eight series of quinazolinone derivatives and evaluated
their anti-phytopathogenic fungal activity. The bioassay results revealed
that compounds KZL-15, KZL-22, 5b, 6b, 6c, 8e, and 8f exhibited remarkable antifungal activity in vitro. Especially, compound 6c displayed the highest bioactivity
against Sclerotinia sclerotiorum, Pellicularia sasakii, Fusarium graminearum, and Fusarium oxysporum, displaying
appreciable IC50 values (50% inhibitory concentration)
of 2.46, 2.94, 6.03, and 11.9 μg/mL, respectively. A further
mechanism interrogation revealed abnormal mycelia, damaged organelles,
and changed permeability of cell membranes in S. sclerotiorum treated with compound 6c. In addition, the in vivo bioassay indicated that compound 6c possessed comparable curative and protective effects (87.3 and 90.7%,
respectively) to the positive control azoxystrobin (89.5 and 91.2%,
respectively) at 100 μg/mL concentration against S. sclerotiorum. This work validated the potential
of compound 6c as a new and promising fungicide candidate,
contributing to the exploration of potent antifungal agents.