School of Life Sciences, State Key Laboratory of Biocatalysis and Enzyme Engineering, National & Local Joint Engineering Research Center of High-throughput Drug Screening Technology, Hubei University, Wuhan, PR China.
College of Life Science and Technology, Key Laboratory of Molecular Biophysics of Ministry of Education, National Engineering Research Center for Nanomedicine, Huazhong University of Science and Technology, Wuhan, PR China.
J Enzyme Inhib Med Chem. 2024 Dec;39(1):2411573. doi: 10.1080/14756366.2024.2411573. Epub 2024 Oct 10.
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 .
由 引起的人畜共患病正在严重加剧。但是，常用的抗生素药物往往会导致耐药性。dUTP 酶（dUTPase）在 的增殖中起着关键作用，被认为是一种有效的药物靶标。然而，关于 dUTP 酶抑制剂的报道很少。在这项研究中，我们发现了一系列新型的 dUTP 酶抑制剂来对抗 。首次发布了 dUTP 酶的第一个晶体结构，并进行了基于结构的计算设计。化合物 和 对 dUTP 酶表现出有希望的活性（IC = 0.99 μM 和 0.7 μM）。此外，它们表现出令人满意的抗 活性（MIC 值范围为 0.5 至 2 mg/L）和低细胞毒性，优于批准药物土霉素和氟苯尼考。分子建模研究表明，疏水相互作用可能是配体结合的主要贡献。我们的结果表明，dUTP 酶抑制剂可能是抑制 的一种有用方法。
