Structure-guided discovery of novel dUTPase inhibitors with anti- activity by computational design.

The zoonosis caused by is increasing seriously. But commonly used antibiotic drugs often lead to resistance. dUTPase (dUTPase) plays a key role in the proliferation of , and was regarded as a potent drug target. However, there was little report about the dUTPase inhibitors. In this study, we discovered a series of novel dUTPase inhibitors to fight against . The first crystal structure of dUTPase was released, and a structure-based computational design was performed. Compounds and exhibited promising activities towards dUTPase (IC = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti- activity (MIC value ranges from 0.5 to 2 mg/L) and low cytotoxicity, which were better than approved drugs oxytetracycline and florfenicol. Molecular modelling study indicated that hydrophobic interaction might be the main contribution for ligand binding. Our results suggested that dUTPase inhibitors might be a useful way to repress .