Synthesis and antibiotic activity of oxazolidinone-catechol conjugates against Pseudomonas aeruginosa

• Published in: Organic & biomolecular chemistry 2015-12, Vol.13 (47), p.11567-11579
• Main Authors: Paulen, Aurélie, Gasser, Véronique, Hoegy, Françoise, Perraud, Quentin, Pesset, Bénédicte, Schalk, Isabelle J, Mislin, Gaëtan L A
• Format: Article
• Language: English
• Subjects: Anti-Bacterial Agents - chemical synthesis; Anti-Bacterial Agents - chemistry; Anti-Bacterial Agents - pharmacology; Catechols - chemical synthesis; Catechols - chemistry; Catechols - pharmacology; Chemical Sciences; Humans; Medicinal Chemistry; Microbial Sensitivity Tests; Oxazolidinones - chemical synthesis; Oxazolidinones - chemistry; Oxazolidinones - pharmacology; Pseudomonas aeruginosa - drug effects; Pseudomonas Infections - drug therapy
• ISSN: 1477-0520; 1477-0539
• DOI: 10.1039/c5ob01859e

Pseudomonas aeruginosa is a Gram-negative pathogenic bacterium responsible for severe infections in which resistance to most of the approved families of antibiotics is increasing. Oxazolidinone antibiotics are active against many Gram-positive bacteria, but are only weakly active against Gram-negative pathogens. We describe the synthesis of conjugates between a catechol moiety and oxazolidinone antibiotics. These conjugates were significantly more active against P. aeruginosa (218-1024 μM) than linezolid (MIC > 1024 μM), the reference molecule from the oxazolidinone family. Antibiotic activity was slightly higher in medium depleted of iron, suggesting the involvement of a bacterial iron uptake system in this biological activity. The bacterial iron uptake pathway involved in the transport is still to be addressed, but the present data excluded a contribution of the enterobactin transporter PfeA.