Synthesis and antibiotic activity of oxazolidinone-catechol conjugates against Pseudomonas aeruginosa.
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.
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Aurélie
A
Paulen
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Véronique
V
Gasser
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Françoise
F
Hoegy
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Quentin
Q
Perraud
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Bénédicte
B
Pesset
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Isabelle J
IJ
Schalk
Equipe Transport Membranaire Bactérien, Biotechnologie et Signalisation Cellulaire, UMR7242 Université de Strasbourg-CNRS, Pole API, 300 boulevard Sébastien Brant, CS10413, 67412 Illkirch Cedex, France. mislin@unistra.fr.
Gaëtan L A
GL
Mislin
D000900:Anti-Bacterial Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D002396:Catechols / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006801:Humans; D008826:Microbial Sensitivity Tests; D023303:Oxazolidinones / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*
D000900:Anti-Bacterial Agents; D002396:Catechols; D023303:Oxazolidinones; C034221:catechol