Open AccessSyntheses of Siderophore–Drug Conjugates Using a Convergent Thiol–Maleimide System
Author(s) -
Raúl E. Juárez-Hernández,
Patricia A. Miller,
Marvin J. Miller
Publication year - 2012
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/ml300150y
Subject(s) - maleimide , conjugate , thiol , combinatorial chemistry , chemistry , drug , siderophore , biochemistry , organic chemistry , pharmacology , medicine , mathematical analysis , mathematics , gene
Three siderophore-drug conjugates (sideromycins) were synthesized by preparation of a maleimide linked derivative of the siderophore desferrioxamine B and reacting the corresponding Ga(3+)-complex with freshly prepared thiol-containing antibiotics: loracarbef, ciprofloxacin and nadifloxacin. The conjugates and their synthetic precursors were tested against a broad panel of bacteria and were found to display Gram-positive selective, growth inhibitory activity (µM) indicating that this approach is suitable for the convergent synthesis and screening of novel sideromycins.