INHIBITORY-ACTION OF YJA2-379, A NEW PROTON PUMP INHIBITOR OF HELICOBACTER-PYLORI GROWTH AND UREASE

The activities of two types of antiulcer agents against 9 strains of H elicobacter pylori (H. pylori) were determined by the agar dilution me thod. The antiulcer agents were YJA20379, a newly synthesized proton p ump inhibitor developed by Yung-Jin Pharmaceutical company, and omepra zole. Both compounds were found to have significant activities against this organism. The MIC values of YJA20379 and omeprazole were 11.7 an d 31.25 mu g/ml, respectively. In addition, the inhibitory potency oi bath compounds was investigated on H. pylori urease which is believed to be an important colonization and virulence factor in the pathogenes is of gastritis and peptic ulcers. These compounds dose-dependently in hibited urease extracted with distilled water and their IC50 values we re 16.4 x 10(-5) M and 14.3 x 10(-5) M, respectively. In addition, a p H-dependent study to determine whether inhibitory potency would be act ivated by acid condition was performed. It was found that unlike omepr azole, YJA20379 was not affected by acid condition. To determine the i nhibition pattern and optimal concentration of substrate, kinetics wer e evaluated at various pH levels (pH 5.0, 7.0, and 8.5). The data show that YJA20379 noncompetitively inhibited H. pylori urease and K-m/K-i values were 0.96 mM/60 mu M (pH 5.0), 0.56 mM/141.5 mu M (pH 7.0), an d 1.94 mM/34 mu M (pH 8.5), respectively. Based on data obtained, it i s concluded that YJA20379 is a significant inhibitor of H. pylori grow th and urease and therefore, taking these results into consideration, YJA20379 might be a beneficial therapy for gastritis and peptic ulcers induced by H. pylori.