Synthesis and biological evaluation of new acinetoferrin homologues for use as iron transport probes in mycobacteria

    Authors

    R. A. Gardner; G. Ghobrial; S. A. Naser;O. Phanstiel

    Comments

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    Abbreviated Journal Title

    J. Med. Chem.

    Keywords

    DRUG DELIVERY AGENTS; PARATUBERCULOSIS; SIDEROPHORE; CHELATORS; TUBERCULOSIS; ANALOGS; SMEGMATIS; DISEASE; AVIUM; ACID; Chemistry, Medicinal

    Abstract

    Four new acinetoferrin homologues were synthesized using a modular synthetic approach. Two linear and two cyclic imide derivatives were generated and evaluated for growth stimulating behavior in Mycobacterium avium subsp paratuberculosis. The yield for the tandem coupling of a functionalized aminohydroxamic acid motif (2 equiv) to a tert-butyl citrate derivative was significantly improved using DCC and N-hydroxysuccinimide. H-1 NMR spectroscopy (CD3OD) provided a convenient method for monitoring the final imidization step in TFA using the doublet patterns between 2.5 and 3.06 ppm. New protocols demonstrated that only a 20% growth enhancement was observed with M. avium subsp. paratuberculosis using the imide of acinetoferrin. Last, a siderophore from Streptomyces pilosus, deferrioxamine B, was shown to cross-feed M. avium subsp. paratuberculosis with the same efficiency as the more costly, native chelator, mycobactin J.

    Journal Title

    Journal of Medicinal Chemistry

    Volume

    47

    Issue/Number

    20

    Publication Date

    1-1-2004

    Document Type

    Article

    Language

    English

    First Page

    4933

    Last Page

    4940

    WOS Identifier

    WOS:000223928500018

    ISSN

    0022-2623

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