Article Dans Une Revue Journal of Medicinal Chemistry Année : 2025

Toward Dual-Target Glycomimetics against Two Bacterial Lectins to Fight Pseudomonas aeruginosaBurkholderia cenocepacia Infections: A Biophysical Study

Résumé

Chronic lung infections caused by Pseudomonas aeruginosa and Burkholderia cenocepacia pose a severe threat to immunocompromised patients, particularly those with cystic fibrosis. These pathogens often infect the respiratory tract, and available treatments are limited due to antibiotic resistance. Targeting bacterial lectins involved in biofilm formation and host-pathogen interactions represents a promising therapeutic strategy. In this study, we evaluate the potential of synthetic fucosylamides as inhibitors of the two lectins LecB (P. aeruginosa) and BC2L-C-Nt (B. cenocepacia). Using a suite of biophysical assays, we assessed their binding affinities, identifying three β-fucosylamides as promising dual-target ligands, while crystallography studies revealed the atomic basis of these ligands to interact with both bacterial lectins. The emerged classes of compounds represent a solid starting point for the necessary hit-to-lead optimization for future dual inhibitors aiming at the treatment of coinfections with these two bacterial pathogens.

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hal-05061662 , version 1 (09-05-2025)

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Giulia Antonini, Mario Fares, Dirk Hauck, Patrycja Mała, Emilie Gillon, et al.. Toward Dual-Target Glycomimetics against Two Bacterial Lectins to Fight Pseudomonas aeruginosaBurkholderia cenocepacia Infections: A Biophysical Study. Journal of Medicinal Chemistry, 2025, 68 (9), pp.9681 - 9693. ⟨10.1021/acs.jmedchem.5c00405⟩. ⟨hal-05061662⟩
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