Design, synthesis, and evaluation of novel organophosphorus inhibitors of bacterial ureases

Journal of Medicinal Chemistry
Stamatia VassiliouLukasz Berlicki

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.

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Citations

Jun 4, 2013·Journal of Molecular Graphics & Modelling·Umer RashidFarzana Latif Ansari
Jul 26, 2011·Journal of Medicinal Chemistry·Artur MuchaŁukasz Berlicki
Aug 15, 2012·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Barbara KrajewskaMałgorzata Brindell
Aug 13, 2014·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Stefano BeniniStefano Ciurli
Feb 16, 2013·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Stefano BeniniStefano Ciurli
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May 23, 2015·Journal of Peptide Science : an Official Publication of the European Peptide Society·Biyun Sun, Jiaxi Xu
Aug 11, 2010·Journal of Enzyme Inhibition and Medicinal Chemistry·Barbara Krajewska, Małgorzata Brindell
Apr 5, 2011·Expert Opinion on Therapeutic Patents·Paulina Kosikowska, Łukasz Berlicki
Jan 22, 2015·Journal of Biological Inorganic Chemistry : JBIC : a Publication of the Society of Biological Inorganic Chemistry·Muhammad Khawar RaufJamshed Iqbal
Aug 16, 2016·Journal of Medicinal Chemistry·Katarzyna MacegoniukŁukasz Berlicki
Sep 3, 2016·Molecules : a Journal of Synthetic Chemistry and Natural Product Chemistry·José Luis Viveros-CeballosCarlos Cativiela
Aug 24, 2016·Journal of Medical Microbiology·Ewa GrelaAgnieszka Monika Grabowiecka
Feb 27, 2017·Bioorganic & Medicinal Chemistry Letters·Katarzyna MacegoniukŁukasz Berlicki
Mar 22, 2019·Current Protein & Peptide Science·Ritu Kataria, Anurag Khatkar
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Aug 6, 2010·Journal of Medicinal Chemistry·Stamatia VassiliouLukasz Berlicki
Dec 29, 2020·Journal of Medicinal Chemistry·Aikaterini PagoniŁukasz Berlicki
Aug 19, 2020·The Journal of Organic Chemistry·Karen R Winters, Jean-Luc Montchamp
Feb 24, 2015·ACS Medicinal Chemistry Letters·Katarzyna MacegoniukŁukasz Berlicki

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