Synthesis and antibiotic activity of oxazolidinone-catechol conjugates against

• Published in: Organic & biomolecular chemistry 2015-11, 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
• 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. An oxazolidinone antibiotic, conjugated to a catechol moiety, was shown to be at least eight times more active against P. aeruginosa , when compared to the linezolid, used as a reference compound.