Academic Journal
Structure-activity studies reveal efficient inactivation of urease by Ebsulfur-based compounds.
| Τίτλος: | Structure-activity studies reveal efficient inactivation of urease by Ebsulfur-based compounds. |
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| Συγγραφείς: | Mazzei L; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, I-40138 Bologna, Italy. Electronic address: luca.mazzei2@unibo.it., Paul A; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, I-40138 Bologna, Italy. Electronic address: arundhati.paul2@unibo.it., Cianci M; Department of Agricultural, Food and Environmental Sciences, Polytechnic University of Marche, I-60131 Ancona, Italy. Electronic address: m.cianci@staff.univpm.it., Pizzi A; Department of Chemistry, Materials, and Chemical Engineering 'Giulio Natta', Politecnico di Milano, I-20131 Milano, Italy. Electronic address: andrea.pizzi@polimi.it., Resnati G; Department of Chemistry, Materials, and Chemical Engineering 'Giulio Natta', Politecnico di Milano, I-20131 Milano, Italy. Electronic address: giuseppe.resnati@polimi.it., Ciurli S; Laboratory of Bioinorganic Chemistry, Department of Pharmacy and Biotechnology (FaBiT), University of Bologna, I-40138 Bologna, Italy. Electronic address: stefano.ciurli@unibo.it. |
| Πηγή: | Journal of inorganic biochemistry [J Inorg Biochem] 2026 Jun; Vol. 279, pp. 113272. Date of Electronic Publication: 2026 Feb 21. |
| Τύπος έκδοσης: | Journal Article |
| Γλώσσα: | English |
| Στοιχεία περιοδικού: | Publisher: Elsevier Country of Publication: United States NLM ID: 7905788 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 1873-3344 (Electronic) Linking ISSN: 01620134 NLM ISO Abbreviation: J Inorg Biochem Subsets: MEDLINE |
| Imprint Name(s): | Original Publication: New York, Elsevier. |
| Ιατρικοί όροι (MeSH): | Urease*/antagonists & inhibitors , Urease*/chemistry , Sporosarcina*/enzymology , Azoles*/chemistry , Azoles*/pharmacology , Organoselenium Compounds*/chemistry , Organoselenium Compounds*/pharmacology , Canavalia*/enzymology , Enzyme Inhibitors*/chemistry , Enzyme Inhibitors*/pharmacology, Isoindoles ; Structure-Activity Relationship ; Crystallography, X-Ray |
| Περίληψη: | Antimicrobial resistance is one of the most significant global health threats of the 21st century, demanding urgent strategies for the development of novel therapeutic approaches. Urease, a nickel-dependent enzyme absent in the human proteome, represents an attractive target for drug development because several urease-expressing bacterial pathogens play a critical role in pathogenesis. Alternative strategies, such as drug repurposing, are necessary to uncover the potential of antimicrobial molecules. In this context, the organo‑selenium compound Ebselen has shown promising urease-inhibitory properties, but its therapeutic application is limited by toxicity concerns. Ebsulfur, a sulfur analog of Ebselen, offers a potentially safer alternative. In this study, we evaluated three Ebsulfur derivatives for their ability to inhibit urease from Sporosarcina pasteurii and Canavalia ensiformis. Biochemical assays demonstrated that these compounds effectively inactivate both bacterial and plant urease in the low micromolar range. The X-ray crystal structures of Sporosarcina pasteurii urease co-crystallized with two of the derivatives, determined at 1.95-1.96 Å resolution, suggested a mechanism involving di‑sulfuration of the catalytically essential αCys322 residue. These findings provide insight into the potential of Ebsulfur derivatives as antimicrobial agents, addressing the persistent lack of progress in antibiotic development, and contribute to the development of alternative antimicrobial strategies targeting resistant pathogens. (Crown Copyright © 2026. Published by Elsevier Inc. All rights reserved.) |
| Competing Interests: | Declaration of competing interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper. |
| Contributed Indexing: | Keywords: Enzyme kinetics; Inhibition; Nickel; Sulfur; Urease; X-ray crystallography |
| Substance Nomenclature: | EC 3.5.1.5 (Urease) 0 (Azoles) 0 (Organoselenium Compounds) 0 (Isoindoles) 40X2P7DPGH (ebselen) 0 (Enzyme Inhibitors) |
| SCR Organism: | Sporosarcina pasteurii |
| Entry Date(s): | Date Created: 20260306 Date Completed: 20260710 Latest Revision: 20260710 |
| Update Code: | 20260711 |
| DOI: | 10.1016/j.jinorgbio.2026.113272 |
| PMID: | 41791238 |
| Βάση Δεδομένων: | MEDLINE |
| ISSN: | 1873-3344 |
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| DOI: | 10.1016/j.jinorgbio.2026.113272 |