Protein translocation is essential for bacterial survival and the most important translocation mechanism is the secretion (Sec) pathway in which SecA is a central core driving force. Thus targeting SecA is a promising strategy for developing novel antibacterial therapeutics. Herein, we report the syntheses and evaluation of a series of nearly 60 4-oxo-5-cyano thiouracil derivatives based upon our previously reported core pyrimidine structure. Introduction of polar group such as –N₃ and linker groups such as –CH₂–O– enhanced the potency several fold. Apart from being potential antibacterial agents, these inhibitors can be indispensable tools for biologists to probe the mechanism of protein translocation via the SecA machinery in bacteria.

蛋白质易位对于细菌存活至关重要，最重要的易位机制是分泌（Sec）途径，其中SecA是核心核心驱动力。因此，靶向SecA是开发新型抗菌疗法的有前途的策略。本文中，我们根据先前报道的核心嘧啶结构，报告了一系列近60种4-氧代-5-氰基硫脲嘧啶衍生物的合成和评价。引入极性基团（例如-N _3）和连接基团（例如-CH ₂ -O-）可以使效力提高数倍。这些抑制剂除了是潜在的抗菌剂外，还可以作为生物学家通过细菌中的SecA机制探查蛋白质转运机制的必不可少的工具。