Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice

Antimicrob Agents Chemother. 2013 Oct;57(10):5138-40. doi: 10.1128/AAC.00918-13. Epub 2013 Jul 15.


Mycobactin biosynthesis in Mycobacterium tuberculosis facilitates iron acquisition, which is required for growth and virulence. The mycobactin biosynthesis inhibitor salicyl-AMS [5'-O-(N-salicylsulfamoyl)adenosine] inhibits M. tuberculosis growth in vitro under iron-limited conditions. Here, we conducted a single-dose pharmacokinetic study and a monotherapy study of salicyl-AMS with mice. Intraperitoneal injection yielded much better pharmacokinetic parameter values than oral administration did. Monotherapy of salicyl-AMS at 5.6 or 16.7 mg/kg significantly inhibited M. tuberculosis growth in the mouse lung, providing the first in vivo proof of concept for this novel antibacterial strategy.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Anti-Bacterial Agents / pharmacology*
  • Female
  • Lung / drug effects*
  • Lung / metabolism
  • Lung / microbiology
  • Mice
  • Mice, Inbred BALB C
  • Mycobacterium tuberculosis / drug effects*
  • Oxazoles / metabolism*
  • Random Allocation


  • Anti-Bacterial Agents
  • Oxazoles
  • mycobactins