Inhibitory action of YJA20379, a new proton pump inhibitor onHelicobacter pylori growth and urease
Tóm tắt
The activities of two types of antiulcer agents against 9 strains ofHelicobacter pylori (H. pylori) were determined by the agar dilution method. The antiulcer agents were YJA20379, a newly synthesized proton pump inhibitor developed by Yung-Jin Pharmaceutical company, and omeprazole. Both compounds were found to have significant activities against this organism. The MIC values of YJA20379 and omeprazole were 11.7 and 31.25 µg/ml, respectively. In addition, the inhibitory potency of both compounds was investigated onH. pylori urease which is believed to be an important colonization and virulence factor in the pathogenesis of gastritis and peptic ulcers. These compounds dose-dependently inhibited urease extracted with distilled water and their IC50 values were 16.4×10−5 M and 14.3×10−5 M, respectively. In addition, a pH-dependent study to determine whether inhibitory potency would be activated by acid condition was performed. It was found that unlike omeprazole, YJA20379 was not affected by acid condition. To determine the inhibition pattern and optimal concentration of substrate, kinetics were evaluated at various pH levels (pH 5.0, 7.0, and 8.5). The data show that YJA20379 noncompetitively inhibitedH. pylori urease and KM/Ki values were 0.96 mM/60 µM (pH 5.0), 0.56 mM/141.5 µM (pH 7.0), and 1.94 mM/34 µM (pH 8.5), respectively. Based on data obtained, it is concluded that YJA20379 is a significant inhibitor ofH. pylori growth and urease and therefore, taking these results into consideration, YJA20379 might be a beneficial therapy for gastritis and peptic ulcers induced byH. pylori.
Tài liệu tham khảo
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