Design, Synthesis, and Structure–Activity Relationship of Quinazolinone Derivatives as Potential Fungicides

Abstract

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 <b>KZL-15</b>, <b>KZL-22</b>, <b>5b</b>, <b>6b</b>, <b>6c</b>, <b>8e</b>, and <b>8f</b> exhibited remarkable antifungal activity <i>in vitro</i>. Especially, compound <b>6c</b> displayed the highest bioactivity against <i>Sclerotinia sclerotiorum</i>, <i>Pellicularia sasakii</i>, <i>Fusarium graminearum</i>, and <i>Fusarium oxysporum</i>, 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 <i>S. sclerotiorum</i> treated with compound <b>6c</b>. In addition, the <i>in vivo</i> bioassay indicated that compound <b>6c</b> 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 <i>S. sclerotiorum</i>. This work validated the potential of compound <b>6c</b> as a new and promising fungicide candidate, contributing to the exploration of potent antifungal agents.