Title

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

Authors

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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