Does targeting Arg98 of FimH lead to high affinity antagonists?


Journal

European journal of medicinal chemistry
ISSN: 1768-3254
Titre abrégé: Eur J Med Chem
Pays: France
ID NLM: 0420510

Informations de publication

Date de publication:
05 Feb 2021
Historique:
received: 28 09 2020
revised: 20 11 2020
accepted: 06 12 2020
pubmed: 20 12 2020
medline: 1 5 2021
entrez: 19 12 2020
Statut: ppublish

Résumé

Bacterial resistance has become an important challenge in the treatment of urinary tract infections. The underlying resistance mechanisms can most likely be circumvented with an antiadhesive approach, antagonizing the lectin FimH located at the tip of fimbriae of uropathogenic E. coli. Here we report on a novel series of FimH antagonists based on the 1-(α-d-mannopyranosyl)-4-phenyl-1,2,3-triazole scaffold, designed to incorporate carboxylic acid or ester functions to interact with FimH Arg98. The most potent representative of the series, ester 11e, displayed a K

Identifiants

pubmed: 33340913
pii: S0223-5234(20)31065-5
doi: 10.1016/j.ejmech.2020.113093
pii:
doi:

Substances chimiques

Adhesins, Escherichia coli 0
fimH protein, E coli 0
Fimbriae Proteins 147680-16-8

Types de publication

Journal Article

Langues

eng

Sous-ensembles de citation

IM

Pagination

113093

Informations de copyright

Copyright © 2020 Elsevier Masson SAS. 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.

Auteurs

Tihomir Tomašič (T)

University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000, Ljubljana, Slovenia.

Said Rabbani (S)

Molecular Pharmacy Group, Department of Pharmaceutical Sciences, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.

Roman P Jakob (RP)

Institute of Structural Biology, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland.

Andreas Reisner (A)

Biomedical Science, University of Applied Sciences, Graz, Austria.

Žiga Jakopin (Ž)

University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000, Ljubljana, Slovenia.

Timm Maier (T)

Institute of Structural Biology, University of Basel, Klingelbergstrasse 70, 4056, Basel, Switzerland.

Beat Ernst (B)

Molecular Pharmacy Group, Department of Pharmaceutical Sciences, Pharmacenter, University of Basel, Klingelbergstrasse 50, 4056, Basel, Switzerland.

Marko Anderluh (M)

University of Ljubljana, Faculty of Pharmacy, Aškerčeva 7, 1000, Ljubljana, Slovenia. Electronic address: marko.anderluh@ffa.uni-lj.si.

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Classifications MeSH