柑橘溃疡病菌(Xanthomonas axonopodis pv. citri, Xac)对我国柑橘生产造成了严重危害。本课题组前期工作发现吡啶基喹唑啉酮类化合物C1对Xac具有良好的抑制活性。但是，C1抑制柑橘溃疡病菌的作用机制、其作用分子靶标尚不明确。为了探究C1的作用机制，本申请拟开展以下四部分工作：1）通过电镜及生物学实验，初步探讨C1对Xac的抑菌作用机理；2）采用蛋白组学、生物信息学、分子生物学方法，寻找C1抑制Xac的关键靶标蛋白1~2个；3）通过体外原核表达方式获得靶标蛋白，建立化学生物学研究平台，确定靶标蛋白与C1之间的作用模式；4）设计合成一系列新型吡啶基喹唑啉酮衍生物，测试目标化合物对Xac的离体生物活性，采用建立的化学生物学研究平台，探究高活性化合物与靶标蛋白的相互作用，期望获得更高活性的新结构化合物1~2个。

Citrus canker (Xanthomonas axonopodis pv. citri, Xac) has caused serious harm to citrus production in China. In our previous work, quinazolinone compound containing pyridine moiety C1 was found to possess good inhibitory activity on Xac. However, the mechanism and molecular target of C1 inhibiting Xac is unclear. This proposal aims to elucidate the action mechanism of Xac against C1, and the main research plans are as following. 1) Preliminarily exploration of the antibacterial action mechanism of Xac against C1 will be carried out through using electronic microscopy as well as other biological experimental methods. 2) Target identification of C1 in Xac will be studied using proteomic, bioinformatic and molecular biology methods, during which 1-2 target protein is expected to be obtained. 3) Pokaryotic expression of target protein will be carried out and the interaction between active compound C1 and target protein will be investigated. 4) A series of new quinazolinone containing pyridine moiety will be designed and synthesized. The biological activities of the new compounds will be assayed against Xac in vitro. The interaction of highly active compounds and target protein will be evaluated, during which 1-2 more potent new structures are expected to be found out.