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Issue 24, 2011
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Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin

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Abstract

Pyochelin is a siderophore common to Pseudomonas aeruginosa and several other pathogenic bacteria. A pyochelin functionalized at the N3′′ position with a propyl-amine extension was previously synthesized. In the present work we proved that this analog binds FptA, the pyochelin outer membrane receptor, and transports iron(III) efficiently into bacteria. This functionalized pyochelin seemed to be a good candidate for antibiotic vectorization in the framework of a Trojan horse prodrug strategy. In this context, conjugates between pyochelin and three fluoroquinolones (norfloxacin, ciprofloxacin and N-desmethyl-ofloxacin) were synthesized with a spacer arm that was either stable or hydrolyzable in vivo. Some pyochelin–fluoroquinolone conjugates had antibacterial activities in growth inhibition experiments on several P. aeruginosa strains. However, these activities were weaker than those of the antibiotic alone. These properties appeared to be related to both the solubility and bioavailability of conjugates and to the stability of the spacer arm used.

Graphical abstract: Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin

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Publication details

The article was received on 25 Jul 2011, accepted on 14 Sep 2011 and first published on 14 Sep 2011


Article type: Paper
DOI: 10.1039/C1OB06250F
Citation: Org. Biomol. Chem., 2011,9, 8288-8300
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    Synthesis and biological properties of conjugates between fluoroquinolones and a N3′′-functionalized pyochelin

    S. Noël, V. Gasser, B. Pesset, F. Hoegy, D. Rognan, I. J. Schalk and G. L. A. Mislin, Org. Biomol. Chem., 2011, 9, 8288
    DOI: 10.1039/C1OB06250F

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