title: 1,2-Benzisoselenazol-3(2H)-one Derivatives As a New Class of Bacterial Urease Inhibitors.
abstract: Urease inhibitors are considered promising compounds for the treatment of ureolytic bacterial infections, particularly infections resulting from Helicobacter pylori in the gastric tract. Herein, we present the synthesis and the inhibitory activity of novel and highly effective organoselenium compounds as inhibitors of Sporosarcina pasteurii and Helicobacter pylori ureases. These studied compounds represent a class of competitive reversible urease inhibitors. The most active compound, 2-phenyl-1,2-benzisoselenazol-3(2H)-one (ebselen), displayed Ki values equal to 2.11 and 226 nM against S. pasteurii and H. pylori enzymes, respectively, indicating ebselen as one of the most potent low-molecular-weight inhibitors of bacterial ureases reported to date. Most of these molecules penetrated through the cell membrane of the Gram-negative bacteria Escherichia coli (pGEM::ureOP) in vitro. Furthermore, whole-cell studies on the H. pylori J99 reference strain confirmed the high efficiency of the examined organoselenium compounds as urease inhibitors against pathogenic bacteria.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Katarzyna
authors.initials: K
authors.lastname: Macegoniuk
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Grela
authors.affiliation: Department of Organic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Jerzy
authors.initials: J
authors.lastname: Palus
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Ewa
authors.initials: E
authors.lastname: Rudzińska-Szostak
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Grabowiecka
authors.affiliation: Department of Microbiology, Medical University of Wrocław , Tytusa Chałubińskiego 4, 50-368 Wrocław, Poland.
authors.forename: Monika
authors.initials: M
authors.lastname: Biernat
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Łukasz
authors.initials: Ł
authors.lastname: Berlicki
mesh_terms: D001393:Azoles / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D002463:Cell Membrane Permeability; D004926:Escherichia coli / Q000187:drug effects / Q000201:enzymology; D016480:Helicobacter pylori / Q000187:drug effects / Q000201:enzymology; D054833:Isoindoles; D008958:Models, Molecular; D016566:Organoselenium Compounds / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D011994:Recombinant Proteins / Q000378:metabolism; D058644:Sporosarcina / Q000201:enzymology; D014510:Urease / Q000037:antagonists & inhibitors* / Q000737:chemistry / Q000378:metabolism
chemical_list: D001393:Azoles; D001426:Bacterial Proteins; D054833:Isoindoles; D016566:Organoselenium Compounds; D011994:Recombinant Proteins; C042986:ebselen; D014510:Urease