BACKGROUNDTo discover more efficient agricultural antimicrobial agents, a series of new quinazoline derivatives containing both a piperazine linker and the N‐acetyl moiety were prepared and assessed for their antibacterial and antifungal activities.RESULTSAll the target compounds were characterized by 1H and 13C NMR as well as high‐resolution mass spectrometry (HRMS), and the chemical structure of the most potent compound E19 incorporating a 4‐trifluoromethoxy substituent was clearly confirmed via single crystal X‐ray diffraction measurements. The bioassay results indicated that some compounds possessed notable inhibitory effects in vitro against the bacterium Xanthomonas oryzae pv. oryzicola (Xoc). For example, compound E19 had an EC50 (effective concentration for 50% activity) value of 7.1 μg/mL towards this pathogen, approximately 15‐ and 10‐fold more effective than the commercial bactericides thiodiazole copper and bismerthiazol (EC50 = 110.2 and 72.4 μg/mL, respectively). Subsequently, the mechanistic studies showed that compound E19 likely exerted its antibacterial efficacies by altering the cell morphology, increasing the permeability of bacterial cytoplasmic membrane, suppressing the production of bacterial extracellular polysaccharides and the extracellular enzyme activities (amylase and cellulase), and blocking the swimming motility of Xoc. Moreover, the proteomic analysis revealed that compound E19 could reduce the bacterial flagellar biosynthesis and decrease the flagellar motility by down‐regulating the expression of the related differential proteins.CONCLUSIONCompound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry.

中文翻译：

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含有哌嗪连接基和N-乙酰基的新型喹唑啉衍生物的合成和农用抗菌评价


背景为了发现更高效的农用抗菌剂，制备了一系列含有哌嗪连接基和N-乙酰基的新型喹唑啉衍生物，并评估了其抗菌和抗真菌活性。结果所有目标化合物均通过1H和13C NMR以及高分辨率质谱（HRMS），并且通过单晶 X 射线衍射测量清楚地证实了包含 4-三氟甲氧基取代基的最有效化合物 E19 的化学结构。生物测定结果表明，部分化合物对米黄单胞菌（Xanthomonas oryzae pv.）具有显着的体外抑制作用。米兹科拉 (Xoc)。例如，化合物 E19 对此病原体的 EC50（50% 活性有效浓度）值为 7.1 μg/mL，比商业杀菌剂噻二唑铜和双噻唑（EC50 = 110.2 和 72.4 μg）有效约 15 倍和 10 倍。 /mL）。随后的机理研究表明，化合物E19可能通过改变细胞形态、增加细菌细胞质膜的通透性、抑制细菌胞外多糖的产生和胞外酶（淀粉酶和纤维素酶）活性、阻断游动等方式发挥抗菌作用。 Xoc 的运动性。此外，蛋白质组分析表明，化合物E19可以通过下调相关差异蛋白的表达来减少细菌鞭毛生物合成并降低鞭毛运动性。结论化合物E19作为控制Xoc的候选杀菌剂具有进一步开发的良好潜力。 © 2024 化学工业协会。