Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Science and Technology, Wybrzeże Wyspiańskiego 27, 50-370, Wrocław, Poland.
Chem Rec. 2022 Aug;22(8):e202200026. doi: 10.1002/tcr.202200026. Epub 2022 May 3.
Urease, an enzyme that catalyzes the hydrolysis of urea, is a virulence factor of various pathogenic bacteria. In particular, Helicobacter pylori, that colonizes the digestive tract and Proteus spp., that can infect the urinary tract, are related to urease activity. Therefore, urease inhibitors are considered as potential therapeutics against these infections. This review describes current knowledge of the structures, activity, and biological importance of bacterial ureases. Moreover, the structure-based design of several classes of bacterial urease inhibitors is presented and discussed. Phosphinic and phosphonic acids were applied as transition-state analogues, while Michael acceptors and ebselen derivatives were applied as covalent binders of cysteine residue. This review incorporates bacterial urease inhibitors from literature published between 2008 and 2021.
脲酶是一种能够催化尿素水解的酶，是多种致病菌的毒力因子。特别是定植于消化道的幽门螺杆菌和可感染泌尿道的变形杆菌属，与脲酶活性有关。因此，脲酶抑制剂被认为是治疗这些感染的潜在药物。本综述描述了细菌脲酶的结构、活性和生物学重要性的现有知识。此外，还介绍和讨论了基于结构的几类细菌脲酶抑制剂的设计。膦酸和次膦酸被用作过渡态类似物，而迈克尔受体和依布硒啉衍生物被用作半胱氨酸残基的共价结合物。本综述纳入了 2008 年至 2021 年期间文献中报道的细菌脲酶抑制剂。
