1. The synthesis and evaluation of phenoxyacylhydroxamic acids as potential agents for Helicobacter pylori infections.
- Author
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Ni WW, Liu Q, Ren SZ, Li WY, Yi LL, Jing H, Sheng LX, Wan Q, Zhong PF, Fang HL, Ouyang H, Xiao ZP, and Zhu HL
- Subjects
- Anti-Bacterial Agents chemical synthesis, Anti-Bacterial Agents chemistry, Dose-Response Relationship, Drug, Drug Design, Enzyme Inhibitors chemical synthesis, Enzyme Inhibitors chemistry, Helicobacter Infections metabolism, Helicobacter pylori cytology, Helicobacter pylori enzymology, Hydroxamic Acids chemical synthesis, Hydroxamic Acids chemistry, Kinetics, Microbial Sensitivity Tests, Molecular Docking Simulation, Molecular Structure, Structure-Activity Relationship, Urease isolation & purification, Urease metabolism, Anti-Bacterial Agents pharmacology, Enzyme Inhibitors pharmacology, Helicobacter Infections drug therapy, Helicobacter pylori drug effects, Hydroxamic Acids pharmacology, Urease antagonists & inhibitors
- Abstract
Two series of ω-phenoxy contained acylhydroxamic acids as novel urease inhibitors were designed and synthesized. Biological activity evaluations revealed that ω-phenoxypropinoylhydroxamic acids were more active than phenoxyacetohydroxamic acids. Out of these compounds, 3-(3,4-dichlorophenoxy)propionylhydroxamic acid c24 showed significant potency against urease in both cell free extract (IC
50 = 0.061 ± 0.003 μM) and intact cell (IC50 = 0.89 ± 0.05 μM), being over 450- and 120-fold more potent than the clinically prescribed urease inhibitor AHA, repectively. Non-linear fitting of experimental data (V-[S]) suggested a mixed-type inhibition mechanism and a dual site binding mode of these compounds., (Copyright © 2018 Elsevier Ltd. All rights reserved.)- Published
- 2018
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