含喹唑啉结构的苯甲酰胺类衍生物合成及抗菌活性  

Synthesis and antibacterial activity of benzamide derivatives containing quinazoline moiety

作　　者：刘莹[1] 徐勇 田立 LIU Ying;XU Yong;TIAN Li(Department of Food Science and Engineering Guiyang University,Guiyang 550005,China)

机构地区：[1]贵阳学院食品科学与工程学院,贵州贵阳550005

出　　处：《化学研究与应用》2024年第1期81-91,共11页Chemical Research and Application

基　　金：贵州省科技计划项目(黔科合基础[2019] 1130号)资助。

摘　　要：以溴代邻氨基苯甲酸为原料,运用活性结构拼接法,设计合成了17个新型的含喹唑啉结构的苯甲酰胺类衍生物(Ⅳ_(a)~Ⅳ_(q))。通过~1H NMR、^(13)C NMR、HRMS和元素分析对化合物进行了结构确认,并以叶枯唑为阳性对照药物,分别在50μg·mL^(-1)、100μg·mL^(-1)浓度下,测试了所有产物对3种常见植物细菌(水稻白叶枯细菌(Xoo)、猕猴桃溃疡病菌(Psa)、柑橘溃疡病菌(Xac))的体外抗菌活性。由于化合物Ⅳ_(d)在两个浓度时对3种细菌抑菌率普遍高于其他16个化合物,且对水稻白叶枯细菌(Xoo)的抑菌率高达100%,明显高于化合物Ⅳ_(d)对另外2种细菌的抑菌率,因此对化合物Ⅳ_(d)进行了抗水稻白叶枯细菌(Xoo)作用机制研究。结果表明:大部分目标化合物对三种病菌都具有一定的抑制活性,其中化合物Ⅳ_(d)表现出较好的抑菌作用。在菌体浓度为10~8CFU/mL,化合物Ⅳ_(d)对Xoo的最低抑菌浓度(MIC)为100μg·mL^(-1),化合物Ⅳ_(d)可通过改变Xoo细胞膜的通透性,在一定程度上破坏菌体的细胞膜,使病原菌细胞内的蛋白质发生泄露,并且化合物Ⅳ_(d)浓度越高,对细胞膜通透性的影响越大;当目标化合物Ⅳ_(d)浓度达到2MIC时,可显著降低3种关键菌体胞内酶活性,从而影响Xoo菌体正常的能量代谢,起到抑菌作用。17 benzamide derivatives containing quinazoline structures(Ⅳa~Ⅳq)were synthesized by using bromine adjacent aminobenzilic acid as raw material,and the compounds were structure confirmed by ^(1)H NMR,^(13)C HRMS and elemental analysis.And with lexazole as positive control drug,the in vitro antibacterial activity of all products was tested against three common plant bacteria(Xanthomonas oryzae pv.Oryzae(Xoo)、Pseudomonas syringae(Psa)、Xanthomonas axonopodis pv.citri(Xac)at 50μ·mL^(-1) and 100μg·mL^(-1).Since compound Ⅳ_(d) of three bacteria was generally higher than that of the other 16 compounds,and the antibacterial rate of Xoo was up to 100%,which was significantly higher than that of compound Ⅳ_(d),the mechanism of action of Xoo was studied.The results showed that most of the target compounds had some inhibitory activity against the three bacteria,the compound Ⅳ_(d) showed a better antibacterial effect.When the bacterial concentration was 10~8 CFU/mL,the minimum inhibitory concentration(MIC)of compound Ⅳ_(d) to Xoo was 100μg·mL^(-1).In addition,compound IVd could change the permeability of Xoo cell membrane,destroy the cell membrane to a certain extent,leak the protein in the pathogenic cells,and the higher the concentration of compound Ⅳ_(d),the greater the impact on the cell membrane permeability.When the concentration of the target compound Ⅳ_(d) was 2 MIC,it could significantly reduce the intracellular enzyme activities of the three key bacterias,thus affecting the normal energy metabolism of Xoo bacteria and has antibacterial effects.

关 键 词：喹唑啉 苯甲酰胺类衍生物 合成 抗菌活性 抑菌机制 

分 类 号：O626[理学—有机化学]