[4.3.1]Bicyclic FKBP Ligands Inhibit Legionella Pneumophila Infection by LpMip-Dependent and LpMip-Independent Mechanisms.
Antiinfective
Inhibitors
Isomerases
Legionella pneumophila
Medicinal chemistry
Journal
Chembiochem : a European journal of chemical biology
ISSN: 1439-7633
Titre abrégé: Chembiochem
Pays: Germany
ID NLM: 100937360
Informations de publication
Date de publication:
02 11 2023
02 11 2023
Historique:
revised:
24
07
2023
received:
14
06
2023
medline:
3
11
2023
pubmed:
25
7
2023
entrez:
25
7
2023
Statut:
ppublish
Résumé
Legionella pneumophila is the causative agent of Legionnaires' disease, a serious form of pneumonia. Its macrophage infectivity potentiator (Mip), a member of a highly conserved family of FK506-binding proteins (FKBPs), plays a major role in the proliferation of the gram-negative bacterium in host organisms. In this work, we test our library of >1000 FKBP-focused ligands for inhibition of LpMip. The [4.3.1]-bicyclic sulfonamide turned out as a highly preferred scaffold and provided the most potent LpMip inhibitors known so far. Selected compounds were non-toxic to human cells, displayed antibacterial activity and block bacterial proliferation in cellular infection-assays as well as infectivity in human lung tissue explants. The results confirm [4.3.1]-bicyclic sulfonamides as anti-legionellal agents, although their anti-infective properties cannot be explained by inhibition of LpMip alone.
Identifiants
pubmed: 37489700
doi: 10.1002/cbic.202300442
doi:
Substances chimiques
Tacrolimus Binding Proteins
EC 5.2.1.-
Peptidylprolyl Isomerase
EC 5.2.1.8
Bacterial Proteins
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e202300442Informations de copyright
© 2023 The Authors. ChemBioChem published by Wiley-VCH GmbH.
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