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 Ramses Bishai

Research output: Contribution to journalArticle

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 2013

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Pharmacokinetics
Tuberculosis
Iron
Growth
Intraperitoneal Injections
Mycobacterium tuberculosis
Adenosine
Oral Administration
Virulence
Lung
mycobactins
In Vitro Techniques

ASJC Scopus subject areas

  • Pharmacology (medical)
  • Pharmacology
  • Infectious Diseases

Cite this

Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice. / Lun, Shichun; Guo, Haidan; Adamson, John; Cisar, Justin S.; Davis, Tony D.; Chavadi, Sivagami Sundaram; Warren, J. David; Quadri, Luis E N; Tan, Derek S.; Bishai, William Ramses.

In: Antimicrobial Agents and Chemotherapy, Vol. 57, No. 10, 10.2013, p. 5138-5140.

Research output: Contribution to journalArticle

Lun, S, Guo, H, Adamson, J, Cisar, JS, Davis, TD, Chavadi, SS, Warren, JD, Quadri, LEN, Tan, DS & Bishai, WR 2013, 'Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice', Antimicrobial Agents and Chemotherapy, vol. 57, no. 10, pp. 5138-5140. https://doi.org/10.1128/AAC.00918-13
Lun, Shichun ; Guo, Haidan ; Adamson, John ; Cisar, Justin S. ; Davis, Tony D. ; Chavadi, Sivagami Sundaram ; Warren, J. David ; Quadri, Luis E N ; Tan, Derek S. ; Bishai, William Ramses. / Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice. In: Antimicrobial Agents and Chemotherapy. 2013 ; Vol. 57, No. 10. pp. 5138-5140.
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