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

ABSTRACT: The zoonosis caused by Nocardia is increasing seriously. But commonly used antibiotic drugs often lead to resistance. N. seriolae dUTPase (NsdUTPase) plays a key role in the proliferation of Nocardia, and was regarded as a potent drug target. However, there was little report about the NsdUTPase inhibitors. In this study, we discovered a series of novel NsdUTPase inhibitors to fight against Nocardia. The first crystal structure of NsdUTPase was released, and a structure-based computational design was performed. Compounds 4b and 12b exhibited promising activities towards NsdUTPase (IC₅₀ = 0.99 μM and 0.7 μM). In addition, they showed satisfied anti-Nocardia activity (MIC value ranges from 0.5 to 2 

SUBMITTER: Wang ZZ 

PROVIDER: S-EPMC11486130 | biostudies-literature | 2024 Dec

REPOSITORIES: biostudies-literature