Synthesis and biological evaluation of triazolyl-substituted benzyloxyacetohydroxamic acids as LpxC inhibitors.
Amidohydrolases
/ antagonists & inhibitors
Anti-Bacterial Agents
/ chemical synthesis
Bacterial Proteins
/ antagonists & inhibitors
Cycloaddition Reaction
Enzyme Inhibitors
/ chemical synthesis
Gram-Negative Bacteria
/ drug effects
Humans
Hydroxamic Acids
/ chemical synthesis
Microbial Sensitivity Tests
Molecular Docking Simulation
Molecular Structure
Stereoisomerism
Structure-Activity Relationship
Triazoles
/ chemistry
Azide-alkyne cycloadditions
Enantioselective synthesis
Hydroxamic acids
LpxC inhibitors
Structure-activity relationships
Triazole derivatives
Journal
Bioorganic & medicinal chemistry
ISSN: 1464-3391
Titre abrégé: Bioorg Med Chem
Pays: England
ID NLM: 9413298
Informations de publication
Date de publication:
01 07 2020
01 07 2020
Historique:
received:
20
03
2020
revised:
20
04
2020
accepted:
21
04
2020
pubmed:
11
5
2020
medline:
24
3
2021
entrez:
11
5
2020
Statut:
ppublish
Résumé
The bacterial deacetylase LpxC is a promising target for the development of antibiotics selectively combating Gram-negative bacteria. To improve the biological activity of the reported benzyloxyacetohydroxamic acid 9 ((S)-N-hydroxy-2-{2-hydroxy-1-[4-(phenylethynyl)phenyl]ethoxy}acetamide), its hydroxy group was replaced by a triazole ring. Therefore, in divergent syntheses, triazole derivatives exhibiting rigid and flexible lipophilic side chains, different configurations at their stereocenter, and various substitution patterns at the triazole ring were synthesized, tested for antibacterial and LpxC inhibitory activity, and structure-activity relationships were deduced based on docking and binding energy calculations.
Identifiants
pubmed: 32386952
pii: S0968-0896(20)30355-2
doi: 10.1016/j.bmc.2020.115529
pii:
doi:
Substances chimiques
Anti-Bacterial Agents
0
Bacterial Proteins
0
Enzyme Inhibitors
0
Hydroxamic Acids
0
Triazoles
0
acetohydroxamic acid
4RZ82L2GY5
Amidohydrolases
EC 3.5.-
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
115529Informations de copyright
Copyright © 2020 Elsevier Ltd. All rights reserved.
Déclaration de conflit d'intérêts
Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.