Synthesis and biological evaluation of new acinetoferrin homologues for use as iron transport probes in mycobacteria.
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. (1)H NMR spectroscopy (CD(3)OD) 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.
Gardner
Richard A
RA
Department of Chemistry and Department of Molecular Biology and Microbiology, University of Central Florida, Orlando, Florida 32816-2366, USA.
Ghobrial
George
G
Naser
Saleh A
SA
Phanstiel
Otto
O
D001671:Biochemistry / Q000379:methods*; D001692:Biological Transport / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002951:Citrates / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D003676:Deferoxamine / Q000378:metabolism / Q000494:pharmacology; D004353:Drug Evaluation, Preclinical / Q000379:methods; D006877:Hydroxamic Acids / Q000737:chemistry* / Q000378:metabolism / Q000494:pharmacology; D007501:Iron / Q000378:metabolism*; D007502:Iron Chelating Agents / Q000737:chemistry / Q000494:pharmacology; D009682:Magnetic Resonance Spectroscopy / Q000379:methods; D009161:Mycobacterium / Q000187:drug effects / Q000378:metabolism*; D009162:Mycobacterium avium / Q000187:drug effects / Q000378:metabolism; D016927:Mycobacterium avium subsp. paratuberculosis / Q000187:drug effects / Q000254:growth & development / Q000378:metabolism; D010080:Oxazoles / Q000378:metabolism / Q000494:pharmacology
D002951:Citrates; D006877:Hydroxamic Acids; D007502:Iron Chelating Agents; D010080:Oxazoles; C086668:acinetoferrin; C018608:mycobactins; D007501:Iron; D003676:Deferoxamine