The rapid emergence of antibiotic resistance has become a prevalent threat to public health, thereby development of new antibacterial agents having novel mechanisms of action is in an urgent need. Targeting at the cytoskeletal cell division protein filamenting temperature-sensitive mutant Z (FtsZ) has been validated as an effective and promising approach for antibacterial drug discovery. In this study, a series of novel biphenyl-benzamides as FtsZ inhibitors has been rationally designed, synthesized and evaluated for their antibacterial activities against various Gram-positive bacteria strains. In particular, the most promising compound 30 exhibited excellent antibacterial activities, especially against four different Bacillus subtilis strains, with an MIC range of 0.008 μg/mL to 0.063 μg/mL. Moreover, compound 30 also showed good pharmaceutical properties with low cytotoxicity (CC₅₀ > 20 μg/mL), excellent human metabolic stability (T_1/2 = 111.98 min), moderate pharmacokinetics (T_1/2 = 2.26 h, F = 61.2%) and in vivo efficacy, which can be identified as a promising FtsZ inhibitor worthy of further profiling.

抗生素耐药性的迅速出现已成为对公众健康的普遍威胁，因此迫切需要开发具有新作用机制的新型抗菌剂。针对细胞骨架细胞分裂蛋白丝状温度敏感突变体 Z (FtsZ) 已被证实是一种有效且有前景的抗菌药物发现方法。本研究合理设计、合成了一系列新型联苯-苯甲酰胺作为 FtsZ 抑制剂，并评估了它们对各种革兰氏阳性菌的抗菌活性。特别是，最有前途的化合物30表现出优异的抗菌活性，尤其是对四种不同的枯草芽孢杆菌菌株，MIC 范围为 0.008 μg/mL 至 0.063 μg/mL。此外，化合物30还表现出良好的药学性质，具有低细胞毒性（CC ₅₀  > 20 μg/mL）、优异的人体代谢稳定性（T _1/2  = 111.98 min）、适中的药代动力学（T _1/2  = 2.26 h，F = 61.2） %）和体内功效，这可以被确定为一种有前途的 FtsZ 抑制剂，值得进一步分析。