3-Arylpropionylhydroxamic acid derivatives as Helicobacter pylori urease inhibitors: Synthesis, molecular docking and biological evaluation.
Bioorg Med Chem
; 24(19): 4519-4527, 2016 10 01.
Article
em En
| MEDLINE
| ID: mdl-27492194
Helicobacter pylori urease is involved in several physiologic responses such as stomach and duodenal ulcers, adenocarcinomas and stomach lymphomas. Thus, inhibition of urease is taken for a good chance to treat H. pylori-caused infections, we have therefore focused our efforts on seeking novel urease inhibitors. Here, a series of arylpropionylhydroxamic acids were synthesized and evaluated for urease inhibition. Out of these compounds, 3-(2-benzyloxy-5-chlorophenyl)-3-hydroxypropionylhydroxamic acid (d24) was the most active inhibitor with IC50 of 0.15±0.05µM, showing a mixed inhibition with both competitive and uncompetitive aspects. Non-linear fitting of kinetic data gives kinetics parameters of 0.13 and 0.12µg·mL(-1) for Ki and Ki', respectively. The plasma protein binding assays suggested that d24 exhibited moderate binding to human and rabbit plasma proteins.
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Base de dados:
MEDLINE
Assunto principal:
Urease
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Helicobacter pylori
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Ácidos Hidroxâmicos
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Antibacterianos
Limite:
Animals
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Humans
Idioma:
En
Ano de publicação:
2016
Tipo de documento:
Article