Document Detail

Large-scale virtual screening for the identification of new Helicobacter pylori urease inhibitor scaffolds.
MedLine Citation:
PMID:  22139480     Owner:  NLM     Status:  MEDLINE    
Here, we report a structure-based virtual screening of the ZINC database (containing about five million compounds) by computational docking and the analysis of docking energy calculations followed by in vitro screening against H. pylori urease enzyme. One of the compounds selected showed urease inhibition in the low micromolar range. Barbituric acid and compounds 1a, 1d, 1e, 1f, 1g, 1h were found to be more potent urease inhibitors than the standard inhibitor hydroxyurea, yielding IC(50) values of 41.6, 83.3, 66.6, 50, 58.8, and 60 μM, respectively (IC(50) of hydroxyurea = 100 μM). 5-Benzylidene barbituric acid has enhanced biological activities compared to barbituric acid. Furthermore, the results indicated that among the substituted 5-benzylidene barbiturates, those with para substitution have higher urease inhibitor activities. This may be because the barbituric acid moiety is closer to the bimetallic nickel center in unsubstituted or para-substituted than in ortho- or meta-substituted analogs, so it has greater chelating ability.
Homa Azizian; Farzaneh Nabati; Amirhossein Sharifi; Farideh Siavoshi; Mohammad Mahdavi; Massoud Amanlou
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2011-12-03
Journal Detail:
Title:  Journal of molecular modeling     Volume:  18     ISSN:  0948-5023     ISO Abbreviation:  J Mol Model     Publication Date:  2012 Jul 
Date Detail:
Created Date:  2012-06-25     Completed Date:  2012-10-22     Revised Date:  2013-03-15    
Medline Journal Info:
Nlm Unique ID:  9806569     Medline TA:  J Mol Model     Country:  Germany    
Other Details:
Languages:  eng     Pagination:  2917-27     Citation Subset:  IM    
Department of Medicinal Chemistry, Faculty of Pharmacy and Pharmaceutical Sciences Research Center, Tehran University of Medical Sciences, 16 Azar Ave, Tehran, Iran.
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MeSH Terms
Barbiturates / chemistry,  metabolism
Catalytic Domain
Computer Simulation
Enzyme Inhibitors / chemistry*,  pharmacology
Helicobacter pylori / drug effects,  enzymology*
Hydrophobic and Hydrophilic Interactions
Inhibitory Concentration 50
Models, Molecular*
Protein Binding
Quantitative Structure-Activity Relationship
Urease / antagonists & inhibitors,  chemistry*,  metabolism
Reg. No./Substance:
0/Barbiturates; 0/Enzyme Inhibitors; EC

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine

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