title: Bis(aminomethyl)phosphinic Acid, a Highly Promising Scaffold for the Development of Bacterial Urease Inhibitors.
abstract: Inhibitors of bacterial ureases are considered to be promising compounds in the treatment of infections caused by Helicobacter pylori in the gastric tract and/or by urealytic bacteria (e.g., Proteus species) in the urinary tract. A new, extended transition state scaffold, bis(aminomethyl)phosphinic acid, was successfully explored for the construction of effective enzyme inhibitors. A reliable methodology for the synthesis of phosphinate analogues in a three-component Mannich-type reaction was elaborated. The obtained molecules were assayed against ureases purified from Sporosarcina pasteurii and Proteus mirabilis, and aminomethyl(N-n-hexylaminomethyl)phosphinic acid was found to be the most potent inhibitor, with a K i = 108 nM against the S. pasteurii enzyme.
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: Anna
authors.initials: A
authors.lastname: Dziełak
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology , Wybrzeże Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors.forename: Artur
authors.initials: A
authors.lastname: Mucha
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
keywords: Mannich-type reaction; inhibitor; urealytic bacteria; ureases