Journal
JOURNAL OF MEDICINAL CHEMISTRY
Volume 57, Issue 24, Pages 10275-10289Publisher
AMER CHEMICAL SOC
DOI: 10.1021/jm500038p
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Funding
- GDR Pseudomonas
- Labex ARCANE
- COST action [BM-1003, CM-1102]
- la Region Rhone-Alpes
- French Fond Unique Interministeriel
- Conseil Regional Rhone-Alpes
- Conseil General des Bouches du Rhone
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Pseudomonas aeruginosa lung infections are a major cause of death in cystic fibrosis and hospitalized patients. Treating these infections is becoming difficult due to the emergence of conventional antimicrobial multiresistance. While monosaccharides have proved beneficial against such bacterial lung infection, the design of several multivalent glycosylated macromolecules has been shown to be also beneficial on biofilm dispersion. In this study, calix[4]arene-based glycoclusters functionalized with galactosides or fucosides have been synthesized. The characterization of their inhibitory properties on Pseudomonas aeruginosa aggregation, biofilm formation, adhesion on epithelial cells, and destruction of alveolar tissues were performed. The antiadhesive properties of the designed glycoclusters were demonstrated through several in vitro bioassays. An in vivo mouse model of lung infection provided an almost complete protection against Pseudomonas aeruginosa with the designed glycoclusters.
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