FtsZ是一种广泛存在于细菌细胞质中的分裂蛋白，在细胞分裂过程中发挥着核心作用。如果FtsZ聚合作用和（或）GTP酶活性受到干扰，将严重影响Z-环形成和隔膜产生，从而导致细菌细胞不能分裂而死亡。因此，以FtsZ为靶点设计、合成新作用机制的抗菌FtsZ抑制剂，是克服日益严重细菌耐药性的一条有效途径。申请人在前期研究的基础上，基于自己提出的新型FtsZ抑制剂设计策略，设计、合成苯甲酰胺类FtsZ抑制剂。通过体内外抗菌活性、细胞分裂抑制活性、FtsZ亲和力、微管蛋白聚合作用和细胞毒性筛选，发现抗菌活性强、选择性高和细胞毒性低的新型FtsZ抑制剂。在此基础上，通过研究新型FtsZ抑制剂对细菌FtsZ聚合作用、GTP酶活性、FtsZ原丝成束、Z-环形成和类核隔离的影响，阐明其抗菌机制。因此，本项目不仅为高效、低毒FtsZ抑制剂的合理设计提供理论依据，而且为全新抗菌机制的创新药物研究奠定基础。

FtsZ is a kind of bacterial cell division protein existed widely in various bacteria and plays a crucial role in the process of the bacterial cell division. If the polymerization and/or GTPase activity of FtsZ are perturbed, the Z-ring and septum formation are inhibited, which leads to bacterial death due to the abnormality of their cell division. Thus, design and synthesis of FtsZ inhibitors with novel antibacterial mechanism based on the FtsZ target is an effective way to overcome the increasing bacterial resistance. On the basis of his previous research, the applicant of this project will design and synthesize antibacterial benzamide FtsZ inhibitors based on the design strategy for the novel FtsZ inhibitors hypothesized by him. Subsequently, the novel FtsZ inhibitors with the potent antibacterial activity, high selectivity and low cytotoxicity will be identified through the evaluation of their in vitro and in vivo antibacterial activity, cell division inhibitory activity, FtsZ affinity, tubulin polymerization and cytotoxicity. Further, antibacterial mechanism of the novel FtsZ inhibitors will be elucidated by investigating their effects on the FtsZ polymerization, the GTPase activity, the FtsZ protofilaments into bundles, the Z-ring formation and the nucleoids segregation. Consequently, the new findings obtained from the above studies will not only provide new ideas for the rational drug design of the FtsZ inhibitors with high efficacy and low cytotoxicity, but also lay the foundation for the research and development of new chemical entities with novel antibacterial mechanism.