Abstract：
BACKGROUND: To 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.
RESULTS: All 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.
CONCLUSIONS: Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry.
RESULTS: All 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.
CONCLUSIONS: Compound E19 exhibited good potential for further development as a bactericide candidate for control of Xoc. © 2024 Society of Chemical Industry.
摘要：
背景：为了发现更有效的农业抗菌剂，制备了一系列包含哌嗪接头和N-乙酰基部分的新喹唑啉衍生物，并评估了它们的抗菌和抗真菌活性。
结果：所有目标化合物均通过1H和13CNMR以及高分辨率质谱（HRMS）进行表征，结合4-三氟甲氧基取代基的最有效的化合物E19的化学结构通过单晶X射线衍射测量清楚地证实。生物测定结果表明，某些化合物在体外对米黄单胞菌pv细菌具有明显的抑制作用。oryzicola（Xoc）。例如,化合物E19对该病原体的EC50（50%活性的有效浓度）值为7.1μg/mL，比商业杀菌剂噻二唑铜和双甲噻唑（EC50=110.2和72.4μg/mL，分别)。随后，机理研究表明，化合物E19可能通过改变细胞形态发挥其抗菌功效，增加细菌细胞质膜的通透性，抑制细菌胞外多糖和胞外酶活性（淀粉酶和纤维素酶）的产生，并阻止Xoc的游泳运动。此外，蛋白质组学分析表明，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的生物合成并降低鞭毛运动。
结论:化合物E19显示出作为用于控制Xoc的候选杀菌剂的进一步开发的良好潜力。©2024化学工业学会。
结果：所有目标化合物均通过1H和13CNMR以及高分辨率质谱（HRMS）进行表征，结合4-三氟甲氧基取代基的最有效的化合物E19的化学结构通过单晶X射线衍射测量清楚地证实。生物测定结果表明，某些化合物在体外对米黄单胞菌pv细菌具有明显的抑制作用。oryzicola（Xoc）。例如,化合物E19对该病原体的EC50（50%活性的有效浓度）值为7.1μg/mL，比商业杀菌剂噻二唑铜和双甲噻唑（EC50=110.2和72.4μg/mL，分别)。随后，机理研究表明，化合物E19可能通过改变细胞形态发挥其抗菌功效，增加细菌细胞质膜的通透性，抑制细菌胞外多糖和胞外酶活性（淀粉酶和纤维素酶）的产生，并阻止Xoc的游泳运动。此外，蛋白质组学分析表明，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的生物合成并降低鞭毛运动。
结论:化合物E19显示出作为用于控制Xoc的候选杀菌剂的进一步开发的良好潜力。©2024化学工业学会。
