Siderophore-Mediated Iron Acquisition: Target for the Development of Selective Antibiotics Towards Mycobacterium tuberculosis - Iron Acquisition by the Genus Mycobacterium - page 73

Fig. 5.10 Truncated mycobactin analogs [ 58 ]
Fig. 5.11 Maleimide-containing mycobactin T analogs [ 61 , 62 ]
[ 61 , 62 ]. In order to perform functionalization through the aryl-oxazoline moiety,
an amino group and a maleimide linker were incorporated at the phenyl ring. The
mycobactin core was not further modified. Screened against replicating M. tuber-
culosis , the synthetic analogs were found to be potent growth inhibitors in the
Microplate Alamar Blue Assay (MABA), 47 (MIC = 0.09 μ M in 7H12 media,
MIC = 0.43 μ M in GAS), 48 (MIC = 0.02 μ M in 7H12 media, MIC = 2.88 μ M
in GAS), 49 (MIC = 0.88 μ M in 7H12 media, MIC = 1.02 μ M in GAS). The
analogs were tested in the Low-Oxygen-Recovery-Assay (LORA) to assess activ-
ity against non-replicating M. tuberculosis (MICs > 50 μ M). More studies are
necessary to determine if the difference in observed activity between both assays
is due to the metabolic needs of the mycobacteria. However, these analogs were
found to be specific inhibitors of M. tuberculosis as no effect was observed when
tested in an agar-diffusion assay against a panel of Gram-positive and Gram-
negative bacteria. While the different levels of activity observed in these analogs,