Synthesis and biological evaluation of new acinetoferrin homologues for use as iron transport probes in mycobacteria
Abbreviated Journal Title
J. Med. Chem.
DRUG DELIVERY AGENTS; PARATUBERCULOSIS; SIDEROPHORE; CHELATORS; TUBERCULOSIS; ANALOGS; SMEGMATIS; DISEASE; AVIUM; ACID; Chemistry, Medicinal
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 of Medicinal Chemistry
"Synthesis and biological evaluation of new acinetoferrin homologues for use as iron transport probes in mycobacteria" (2004). Faculty Bibliography 2000s. 4363.