Pillar[5]arene-Based Polycationic Glyco[2]rotaxanes Designed as Pseudomonas aeruginosa Antibiofilm Agents
Résumé
Pseudomonas aeruginosa is a human pathogen belonging to the top priorities for the discovery of new therapeutic solutions. Its propensity to generate biofilms strongly complicates the treatments required to cure P. aeruginosa infections. Herein we describe the synthesis of a series of novel rotaxanes comprised of a central galactosylated pillar [5]arene, a tetrafucosylated dendron and a tetra-guanidinium subunit. Strategically, we exploited a supramolecular assembly technology to generate complex rotaxanes from relatively simple subcomponents. The final glycorotaxanes displayed high affinity for the two P. aeruginosa lectins LecA and LecB as evaluated by Isothermal Titration Calorimetry. Potent inhibition levels of P. aeruginosa biofilm growth were evidenced showing that the three subunits of the glycorotaxanes work synergistically. Such antibiofilm potency had rarely been reached in the literature. Importantly, none of the final rotaxanes was bactericidal, showing that their antibiofilm activity is lectinmediated but does not depend on bacteria killing, which is a rare feature for antibiofilm agents.
Domaines
Chimie thérapeutique| Origine | Fichiers produits par l'(les) auteur(s) |
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