Marked Reduction of Helicobacter pylori-Induced Gastritis by Urease Inhibitors, Acetohydroxamic Acid and Flurofamide, in Mongolian Gerbils

2001 ◽  
Vol 285 (3) ◽  
pp. 728-733 ◽  
Author(s):  
Toshihisa Ohta ◽  
Hideyuki Shibata ◽  
Toshihiko Kawamori ◽  
Masaki Iimuro ◽  
Takashi Sugimura ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Marked Reduction ◽  
Acetohydroxamic Acid ◽  
Urease Inhibitors ◽  
Mongolian Gerbils

scholarly journals Three-Dimensional Quantitative Structure-Activity Relationship and Comparative Molecular Field Analysis of Dipeptide Hydroxamic Acid Helicobacter pylori Urease Inhibitors

2002 ◽  
Vol 46 (8) ◽  
pp. 2613-2618 ◽  
Author(s):  
Hetal Mishra ◽  
Abby L. Parrill ◽  
John S. Williamson
Keyword(s):  
Helicobacter Pylori ◽  
Hydroxamic Acid ◽  
Field Analysis ◽  
Molecular Field ◽  
Acetohydroxamic Acid ◽  
Urease Inhibitors ◽  
Comparative Molecular Field Analysis ◽  
Comfa Model ◽  
Molecular Field Analysis ◽  
Enzyme Model

ABSTRACT A homology model of Helicobacter pylori urease was developed by using the crystal structure of urease from Klebsiella aerogenes (EC 3.5.1.5) as a template. The acetohydroxamic acid moiety was docked into the active pocket of the enzyme model, followed by relaxation of the complex by use of molecular dynamics. The resulting conformation was used as a template to construct 24 potential dipeptide hydroxamic acid inhibitors with which comparative molecular field analysis (CoMFA) was performed. The resulting model provided a cross-validation correlation coefficient (q 2 L00) of 0.610, a conventional r 2 value of 0.988, and an F (Fisher indication of statistical significance) value of 294.88. We were able to validate the CoMFA model by using the 50% inhibitory concentrations of six compounds that were not included in the construction of the model. A very good structural correlation was observed between the amino acids in the model urease's active pocket and the contour maps derived from the CoMFA model. This correlation, accompanied by the validation supplied by use of the CoMFA data, illustrates that the model can aid in the prediction and design of novel H. pylori urease inhibitors.

Synthesis and Structure−Activity Relationship Studies of N-monosubstituted Aroylthioureas as Urease Inhibitors

2020 ◽  
Vol 16 ◽  
Author(s):  
Wei-Wei Ni ◽  
Hai-Lian Fang ◽  
Ya-Xi Ye ◽  
Wei-Yi Li ◽  
Li Liu ◽  
...  
Keyword(s):  
Regression Analysis ◽  
Mammalian Cells ◽  
Intact Cell ◽  
Linear Regression Analysis ◽  
Positive Control ◽  
Acetohydroxamic Acid ◽  
Urease Inhibitors ◽  
Ic50 Value ◽  
Ic50 Values ◽  
Low Cytotoxicity

Background: Thiourea is a classical urease inhibitor usually as a positive control, and many N,N`-disubstituted thioureas have been determined as urease inhibitors. However, due to steric hindrance, N,N`-disubstituted thiourea motif could not bind urease as thiourea. On the contrary, N-monosubstituted thioureas with a tiny thiourea motif could theoretically bind into the active pocket as thiourea. Objective: A series of N-monosubstituted aroylthioureas were designed and synthesized for evaluation as urease inhibitors. Methods: Urease inhibition was determined by the indophenol method and IC50 values were calculated using computerized linear regression analysis of quantal log dose-probit functions. The kinetic parameters were estimated viasurface plasmon resonance (SPR) and by nonlinear regression analysis based on the mixed type inhibition model derived from Michaelis-Menten kinetics. Results: Compounds b2, b11and b19 reversibly inhibited urease with a mixed mechanism, and showed excellent potency against both cell-free urease and urease in intact cell, with IC50 values being 90-to 450-fold and 5-to 50-fold lower than the positive control acetohydroxamic acid, respectively. The most potent compound b11 showed IC50 value of 0.060 ±0.004μM against cell-free urease, which bound to urea binding site with a very low KDvalue (0.420±0.003nM) and a very long residence time (6.7 min). Compound b11was also demonstrated having very low cytotoxicity to mammalian cells. Conclusion: These results revealed that N-monosubstituted aroylthioureas clearly bind the active site of urease as expected, and represent a new class of urease inhibitors for the development of potential therapeutics against infections caused by ure-ase-containing pathogens.

Effects of Aspirin on the Development of Helicobacter pylori-Induced Gastric Inflammation and Heterotopic Proliferative Glands in Mongolian Gerbils

Helicobacter ◽  
2008 ◽  
Vol 13 (1) ◽  
pp. 20-29 ◽  
Author(s):  
Guo Qing Li ◽  
Harry H. X. Xia ◽  
Min Hu Chen ◽  
Tetsuya Tsukamoto ◽  
Masae Tatematsu ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Mongolian Gerbils

Inhibitory effect of raphanobrassica on Helicobacter pylori-induced gastritis in Mongolian gerbils

2014 ◽  
Vol 70 ◽  
pp. 107-113 ◽  
Author(s):  
Takanori Yamada ◽  
Min Wei ◽  
Takeshi Toyoda ◽  
Shoutaro Yamano ◽  
Hideki Wanibuchi
Keyword(s):  
Helicobacter Pylori ◽  
Inhibitory Effect ◽  
Mongolian Gerbils

A better method for confirming Helicobacter pylori infection in Mongolian gerbils

2008 ◽  
Vol 43 (1) ◽  
pp. 32-37 ◽  
Author(s):  
Chao-Hung Kuo ◽  
Huang-Ming Hu ◽  
Pei-Yun Tsai ◽  
Sheau-Fang Yang ◽  
Lin-Li Chang ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Helicobacter Pylori Infection ◽  
Mongolian Gerbils

scholarly journals Effect of Recombinant CagL Immunization on the Gastric Diseases Induced by Helicobacter pylori in Mongolian gerbils

2012 ◽  
Vol 48 (2) ◽  
pp. 109-115
Author(s):  
Eun-Jung Bak ◽  
Sung-Il Jang ◽  
Yun-Hui Choi ◽  
Jin-Moon Kim ◽  
Ae-Ryun Kim ◽  
...  
Keyword(s):  
Helicobacter Pylori ◽  
Mongolian Gerbils ◽  
Gastric Diseases
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