Affiliation:
1. Department of Bacteriology, Hyogo College of Medicine, Japan.
Abstract
The gastric proton pump inhibitor lansoprazole, its active analog AG-2000, and omeprazole dose dependently inhibited urease activity extracted with distilled water from Helicobacter pylori cells; the 50% inhibitory concentrations were between 3.6 and 9.5 microM, which were more potent than those of urease inhibitors, such as acetohydroxamic acid, hydroxyurea, and thiourea. These compounds also inhibited urease activity in intact cells of H. pylori and Helicobacter mustelae but did not inhibit ureases from other bacteria, such as Proteus vulgaris, Proteus mirabilis, and Providencia rettgeri. The mechanism of urease inhibition was considered to be blockage of the SH groups of H. pylori urease, since SH residues in the enzyme decreased after preincubation with lansoprazole and glutathione or dithiothreitol completely abolished the inhibitory action. The SH-blocking reagents N-ethylmaleimide and idoacetamide were also examined for their inhibition of the urease activity; their 50% inhibitory concentrations were 100- to 1,000-fold higher than those of lansoprazole. These results suggest that lansoprazole and omeprazole can potently and selectively inhibit H. pylori urease and that inhibition may be related to earlier findings indicating that these compounds have selective activity against HP growth.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Cited by
148 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献
1. Rational Design, Synthesis, Docking Simulation, and ADMET Prediction of Novel Barbituric‐hydrazine‐phenoxy‐1,2,3‐triazole‐acetamide Derivatives as Potent Urease Inhibitors;ChemistrySelect;2023-01-17
2. Bis-1,3,4-Oxadiazole Derivatives as Novel and Potential Urease Inhibitors;
Synthesis, In Vitro, and In Silico Studies;Medicinal Chemistry;2022-08
3. Issues Related to the Treatment of H. pylori Infection in People Living with HIV and Receiving Antiretrovirals;Microorganisms;2022-07-29
4. Influence of acotiamide on 13C-urea breath test for Helicobacter pylori diagnosis;Journal of Clinical Biochemistry and Nutrition;2020
5. SYNTHESIS, CHARACTERIZATION AND UREASE INHIBITION STUDIES OF TRANSITION METAL COMPLEXES OF THIOUREAS BEARING IBUPROFEN MOIETY;Journal of the Chilean Chemical Society;2018-06