Antibacterial activity of xylose-derived LpxC inhibitors - Synthesis, biological evaluation and molecular docking studies.


Journal

Bioorganic chemistry
ISSN: 1090-2120
Titre abrégé: Bioorg Chem
Pays: United States
ID NLM: 1303703

Informations de publication

Date de publication:
02 2021
Historique:
received: 12 11 2020
accepted: 24 12 2020
pubmed: 12 1 2021
medline: 7 9 2021
entrez: 11 1 2021
Statut: ppublish

Résumé

LpxC inhibitors represent a promising class of novel antibiotics selectively combating Gram-negative bacteria. In chiral pool syntheses starting from D- and L-xylose, a series of four 2r,3c,4t-configured C-furanosidic LpxC inhibitors was obtained. The synthesized hydroxamic acids were tested for antibacterial and LpxC inhibitory activity, the acquired biological data were compared with those of previously synthesized C-furanosides, and molecular docking studies were performed to rationalize the observed structure-activity relationships. Additionally, bacterial uptake and susceptibility to efflux pump systems were investigated for the most promising stereoisomers.

Identifiants

pubmed: 33429229
pii: S0045-2068(20)31901-5
doi: 10.1016/j.bioorg.2020.104603
pii:
doi:

Substances chimiques

Anti-Bacterial Agents 0
Enzyme Inhibitors 0
Xylose A1TA934AKO
Amidohydrolases EC 3.5.-
UDP-3-O-acyl-N-acetylglucosamine deacetylase EC 3.5.1.-

Types de publication

Journal Article Research Support, Non-U.S. Gov't

Langues

eng

Sous-ensembles de citation

IM

Pagination

104603

Informations de copyright

Copyright © 2020 Elsevier Inc. All rights reserved.

Auteurs

Alexander Dreger (A)

Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.

Katharina Hoff (K)

Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.

Oriana Agoglitta (O)

Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany.

Sven-Kevin Hotop (SK)

Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany.

Mark Brönstrup (M)

Department of Chemical Biology, Helmholtz Centre for Infection Research (HZI), Inhoffenstr. 7, 38124 Braunschweig, Germany; German Center for Infection Research (DZIF), Partner Site Hannover-Braunschweig, Germany.

Peter Heisig (P)

Institute of Biochemistry and Molecular Biology, University of Hamburg, Bundesstr. 45, 20146 Hamburg, Germany.

Johannes Kirchmair (J)

Department of Pharmaceutical Chemistry, University of Vienna, Althanstrasse 14, 1090 Vienna, Austria; Center for Bioinformatics (ZBH), University of Hamburg, Bundesstr. 43, 20146 Hamburg, Germany.

Ralph Holl (R)

Institute of Organic Chemistry, University of Hamburg, Martin-Luther-King-Platz 6, 20146 Hamburg, Germany; German Center for Infection Research (DZIF), Partner Site Hamburg-Lübeck-Borstel-Riems, Germany. Electronic address: ralph.holl@chemie.uni-hamburg.de.

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Classifications MeSH