Background: Considering the interesting role in the peptidoglycan biosynthesis pathway, the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase is an attractive target to develop new antibacterial agents. It catalyzes the first key step of this pathway and its inhibition leads to bacterial cell death. Fosfomycin is known as the natural inhibitor of MurA.

Objective: The study aimed to introduce new inhibitors of MurA by virtual screening of different chemical compounds libraries, and test the best scored “virtual hits” against three pathogenic bacteria: Escherichia coli, Bacillus subtilis and Staphylococcus aureus.

Methods: A virtual screening of the structural analogues of fosfomycin downloaded from the Pub- Chem database was performed. Moreover, French National Chemical Library and ZINC database were also utilized to identify new structures different from fosfomycin. FlexX was the software used for this study. The antibacterial testing was divided into two methods: disk diffusion and broth dilution.

Results: A set of virtual hits was found to have better energy score than that of fosfomycin, seven of them were tested in vitro. In addition, the disk diffusion method explored four compounds that exhibited antibacterial activity: CID-21680357 (fosfomycin analogue), AB-00005001, ZINC04658565, and ZINC901335. The testing was continued by broth dilution method for both compounds CID-21680357 and ZINC901335 to determine their minimum inhibitory concentrations, and ZINC901335 had the best value with 457μg/ml against Staphylococcus aureus.

Conclusion: Four compounds were found and proven in silico and in vitro to have antibacterial activity, namely CID-21680357, AB-00005001, ZINC04658565, and ZINC901335.

背景：考虑到在肽聚糖生物合成途径中的有趣作用，UDP-N-乙酰葡糖胺烯醇丙酮酸转移酶是开发新抗菌剂的有吸引力的目标。它催化该途径的第一个关键步骤，其抑制导致细菌细胞死亡。磷霉素被称为 MurA 的天然抑制剂。

目的：该研究旨在通过虚拟筛选不同的化合物库来引入新的 MurA 抑制剂，并测试针对三种病原菌：大肠杆菌、枯草芽孢杆菌和金黄色葡萄球菌的得分最高的“虚拟命中”。

方法：对从 Pub-Chem 数据库下载的磷霉素结构类似物进行虚拟筛选。此外，还利用法国国家化学图书馆和 ZINC 数据库来识别不同于磷霉素的新结构。FlexX 是用于本研究的软件。抗菌试验分为两种方法：圆片扩散法和肉汤稀释法。

结果：发现一组虚拟命中比磷霉素具有更好的能量评分，其中 7 个进行了体外测试。此外，圆盘扩散法探索了四种具有抗菌活性的化合物：CID-21680357（磷霉素类似物）、AB-00005001、ZINC04658565 和 ZINC901335。通过肉汤稀释法对化合物 CID-21680357 和 ZINC901335 进行测试以确定它们的最低抑菌浓度，ZINC901335 的最佳值是 457μg/ml 对金黄色葡萄球菌。

结论：在计算机模拟和体外实验中发现并证明了四种化合物具有抗菌活性，即 CID-21680357、AB-00005001、ZINC04658565 和 ZINC901335。