Journal
JOURNAL OF MOLECULAR MODELING
Volume 18, Issue 7, Pages 2917-2927Publisher
SPRINGER
DOI: 10.1007/s00894-011-1310-2
Keywords
Helicobacter pylori; Urease inhibitors; Virtual screening; 5-Benzylidene barbituric acid; Docking
Categories
Funding
- Research Council of Tehran University of Medical Sciences
- Iranian National Science Foundation (INSF)
Ask authors/readers for more resources
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 IC50 values of 41.6, 83.3, 66.6, 50, 58.8, and 60 mu M, respectively (IC50 of hydroxyurea = 100 mu M). 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.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available