Design, Synthesis, and Structure-Activity Relationship of Quinazolinone Derivatives as Potential Fungicides
Design, Synthesis, and Structure-Activity Relationship of Quinazolinone Derivatives as Potential Fungicides
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DOI：
10.1021/acs.jafc.0c05475
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发表时间：
2021-04-19
影响因子：
6.1
通讯作者：
Liu, Ying-Qian
中科院分区：
文献类型：
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作者：
Peng, Jing-Wen;Yin, Xiao-Dan;Liu, Ying-Qian
植物病原真菌引起的植物病害降低了作物的产量和品质。为了开发新的抗真菌药物，我们设计并合成了8个系列的喹唑啉酮衍生物，并对它们的抗植物病原真菌活性进行了评价。生物实验结果表明，化合物KZL-15、KZL-22、5b、6b、6c、8e和8f具有明显的体外抗真菌活性。其中，化合物6c对菌核菌、沙氏果皮菌、谷物镰刀菌和尖孢镰刀菌的抑菌活性最高，IC50值（50%抑菌浓度）分别为2.46、2.94、6.03和11.9 μ g/mL。进一步的机制探究发现，化合物6c处理菌丝体异常，细胞器受损，细胞膜通透性改变。此外，体内生物测定表明，化合物6c在100 μ g/mL浓度下对菌核病菌的治疗和保护作用（分别为87.3和90.7%）与阳性对照氮氧嘧菌酯（分别为89.5和91.2%）相当。这一工作验证了化合物6c作为一种新的有前景的杀菌剂候选物的潜力，为开发有效的抗真菌药物做出了贡献。
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 mu g/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 mu g/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.