title: Design, synthesis, and evaluation of novel organophosphorus inhibitors of bacterial ureases.
abstract: A new group of organophosphorus inhibitors of urease, P-methyl phosphinic acids was discovered by using the structure based inhibitor design approach. Several derivatives of the lead compound, aminomethyl(P-methyl)phosphinic acid, were synthesized successfully. Their potency was evaluated in vitro against urease from Bacillus pasteurii and Proteus vulgaris. The studied compounds constitute a group of competitive, reversible inhibitors of bacterial ureases. Obtained thiophosphinic analogues of the most effective structures exhibited kinetic characteristics of potent, slow binding urease inhibitors, with Ki = 170 nM (against B. pasteurii enzyme) for the most active N-( N'-benzyloxycarbonylglycyl)aminomethyl(P-methyl)phosphinothioic acid.
authors: Department of Bioorganic Chemistry, Faculty of Chemistry, Wroclaw University of Technology, Wyb. Wyspiańskiego 27, 50-370 Wrocław, Poland.
authors: Stamatia
authors: S
authors: Vassiliou
authors: Agnieszka
authors: A
authors: Grabowiecka
authors: Paulina
authors: P
authors: Kosikowska
authors: Athanasios
authors: A
authors: Yiotakis
authors: Paweł
authors: P
authors: Kafarski
authors: Łukasz
authors: Ł
authors: Berlicki
mesh_terms: D001407:Bacillus / Q000201:enzymology*; D017076:Computer-Aided Design; D004353:Drug Evaluation, Preclinical; D004791:Enzyme Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D009943:Organophosphorus Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011514:Proteus vulgaris / Q000201:enzymology*; D021241:Spectrometry, Mass, Electrospray Ionization; D014510:Urease / Q000037:antagonists & inhibitors*
chemical_list: D004791:Enzyme Inhibitors; D009943:Organophosphorus Compounds; D014510:Urease