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

Shichun Lun, Haidan Guo, John Adamson, Justin S. Cisar, Tony D. Davis, Sivagami Sundaram Chavadi, J. David Warren, Luis E.N. Quadri, Derek S. Tan, William R. Bishai

Research output: Contribution to journalArticle

34 Scopus citations

Abstract

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] inhibitsM. 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 inhibitedM. tuberculosis growth in the mouse lung, providing the first in vivo proof of concept for this novel antibacterial strategy.

Original languageEnglish (US)
Pages (from-to)5138-5140
Number of pages3
JournalAntimicrobial agents and chemotherapy
Volume57
Issue number10
DOIs
StatePublished - Oct 1 2013

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

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    Lun, S., Guo, H., Adamson, J., Cisar, J. S., Davis, T. D., Chavadi, S. S., Warren, J. D., Quadri, L. E. N., Tan, D. S., & Bishai, W. R. (2013). Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice. Antimicrobial agents and chemotherapy, 57(10), 5138-5140. https://doi.org/10.1128/AAC.00918-13