Inhibitory action of YJA20379, a new proton pump inhibitor on Helicobacter pylori growth and urease.
The activities of two types of antiulcer agents against 9 strains of Helicobacter 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 micrograms/ml, respectively. In addition, the inhibitory potency of both compounds was investigated on H. 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 x 10(-5) M and 14.3 x 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 inhibited H. pylori urease and KM/Ki values were 0.96 mM/60 microM (pH 5.0), 0.56 mM/141.5 microM (pH 7.0), and 1.94 mM/34 microM (pH 8.5), respectively. Based on data obtained, it is concluded that YJA20379 is a significant inhibitor of H. pylori growth and urease and therefore, taking these results into consideration, YJA20379 might be a beneficial therapy for gastritis and peptic ulcers induced by H. pylori.
Woo
T W
TW
Pharmacology and Toxicology Laboratory, Research and Development Center, Kyunggi-Do, Korea.
Chang
M S
MS
Chung
Y K
YK
Kim
K B
KB
Sohn
S K
SK
Kim
S G
SG
Choi
W S
WS
D052160:Benzothiazoles; D004791:Enzyme Inhibitors / Q000494:pharmacology*; D005745:Gastric Acidity Determination; D016480:Helicobacter pylori / Q000187:drug effects* / Q000254:growth & development*; D006863:Hydrogen-Ion Concentration; D007093:Imidazoles / Q000494:pharmacology*; D007700:Kinetics; D008826:Microbial Sensitivity Tests; D009853:Omeprazole / Q000494:pharmacology; D054328:Proton Pump Inhibitors; D013844:Thiazoles / Q000494:pharmacology*; D014510:Urease / Q000037:antagonists & inhibitors* / Q000302:isolation & purification
D052160:Benzothiazoles; D004791:Enzyme Inhibitors; D007093:Imidazoles; D054328:Proton Pump Inhibitors; D013844:Thiazoles; C110270:YJA 20379-1; D014510:Urease; D009853:Omeprazole