title: Computer-aided optimization of phosphinic inhibitors of bacterial ureases.
abstract: Urease inhibitors can be considered as a tool to control the damaging effect of ureolytic bacteria infections in humans which occur commonly in the developed countries. Computer-aided optimization of the aminomethylphosphinate structures by modifying both their N- and P-termini led to the invention of a novel group of inhibitors of bacterial ureases. Introduction of P-hydroxymethyl group into the molecule resulted in considerable increase of the inhibitory activity against enzymes purified from Bacillus pasteurii and Proteus vulgaris as compared with their P-methyl counterparts described previously. The designed compounds represent a competitive reversible class of urease inhibitors. The most potent, N-methyl-aminomethyl-P-hydroxymethylphosphinic acid, displayed K(i) = 360 nM against P. vulgaris enzyme.
authors.affiliation: Department of Bioorganic Chemistry, Faculty of Chemistry, Wrocław University of Technology, Wrocław, Poland.
authors.forename: Stamatia
authors.initials: S
authors.lastname: Vassiliou
authors.forename: Paulina
authors.initials: P
authors.lastname: Kosikowska
authors.forename: Agnieszka
authors.initials: A
authors.lastname: Grabowiecka
authors.forename: Athanasios
authors.initials: A
authors.lastname: Yiotakis
authors.forename: Paweł
authors.initials: P
authors.lastname: Kafarski
authors.forename: Lukasz
authors.initials: L
authors.lastname: Berlicki
mesh_terms: D001407:Bacillus / Q000201:enzymology; D001426:Bacterial Proteins / Q000037:antagonists & inhibitors* / Q000737:chemistry; D003198:Computer Simulation; D004355:Drug Stability; D006868:Hydrolysis; D008958:Models, Molecular; D010721:Phosphinic Acids / Q000138:chemical synthesis* / Q000737:chemistry; D011514:Proteus vulgaris / Q000201:enzymology; D013329:Structure-Activity Relationship; D014510:Urease / Q000037:antagonists & inhibitors* / Q000737:chemistry
chemical_list: D001426:Bacterial Proteins; C551945:N-methyl-aminomethyl-P-hydroxymethylphosphinic acid; D010721:Phosphinic Acids; D014510:Urease