Title

Synthesis and biological evaluation of new citrate-based siderophores as potential probes for the mechanism of iron uptake in mycobacteria

Authors

Authors

H. Y. Guo; S. A. Naser; G. Ghobrial;O. Phanstiel

Abbreviated Journal Title

J. Med. Chem.

Keywords

PARATUBERCULOSIS; TUBERCULOSIS; ANALOGS; SMEGMATIS; DISEASE; AGENTS; AVIUM; Chemistry, Medicinal

Abstract

Several iron chelators containing alpha,beta-unsaturated hydroxamic acid motifs appended to a citric acid platform were synthesized. Mycobacterium paratuberculosis was then challenged to grow in the presence of a panel of siderophores (mycobactin J, deferrioxamine B, acinetoferrin, and nannochelin A) and the new synthetic agents. Of the structures tested, those containing the trans 2-octenoyl motif were preferred over those with trans cinnamoyl groups. In addition, derivatives containing longer tether lengths between the iron binding ligands (C5) were more efficacious and led to higher growth index values. Perhaps most remarkable was the finding that at 2.4 muM a trans 2-octenoylated, citrate-containing imide 6 was nearly 5-fold more effective in stimulating growth than the native chelator, mycobactin J. In this regard, new structural elements were identified (e.g., an imide motif or 2-octenoyl side chain), whose presence stimulated mycobacterial growth.

Journal Title

Journal of Medicinal Chemistry

Volume

45

Issue/Number

10

Publication Date

1-1-2002

Document Type

Article

Language

English

First Page

2056

Last Page

2063

WOS Identifier

WOS:000175488900012

ISSN

0022-2623

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