%0 Journal Article
%T Design, synthesis, and biological evaluation of (thio)urea derivatives as potent Escherichia coli β-glucuronidase inhibitors.
%A Xu K
%A Ying L
%A Ying T
%A Wu Q
%A Du L
%A Yu Y
%A Ying Y
%A Wei B
%A Wang H
%A Yang Z
%J J Enzyme Inhib Med Chem
%V 39
%N 1
%D 2024 Dec
%M 39140677
%F 5.756
%R 10.1080/14756366.2024.2387415
%X EcGUS has drawn considerable attention for its role as a target in alleviating serious GIAEs. In this study, a series of 72 (thio)urea derivatives were designed, synthesised, and biologically assayed. The bioassay results revealed that E-9 (IC50 = 2.68 μM) exhibited a promising inhibitory effect on EcGUS, surpassing EcGUS inhibitor D-saccharic acid-1,4-lactone (DSL, IC50 = 45.8 μM). Additionally, the inhibitory kinetic study indicated that E-9 (Ki = 1.64 μM) acted as an uncompetitive inhibitor against EcGUS. The structure-activity relationship revealed that introducing an electron-withdrawing group into the benzene ring at the para-position is beneficial for enhancing inhibitory activity against EcGUS. Furthermore, molecular docking analysis indicated that E-9 has a strong affinity to EcGUS by forming interactions with residues Asp 163, Tyr 472, and Glu 504. Overall, these results suggested that E-9 could be a potent EcGUS inhibitor, providing valuable insights and guidelines for the development of future inhibitors targeting EcGUS.