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

doi:10.1128/AAC.00918-13

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 journal › Article › peer-review

37 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 language	English (US)
Pages (from-to)	5138-5140
Number of pages	3
Journal	Antimicrobial agents and chemotherapy
Volume	57
Issue number	10
DOIs	https://doi.org/10.1128/AAC.00918-13
State	Published - Oct 2013

ASJC Scopus subject areas

Pharmacology
Pharmacology (medical)
Infectious Diseases

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title = "Pharmacokinetic and in vivo efficacy studies of the mycobactin biosynthesis inhibitor salicyl-AMS in mice",

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.",

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

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AU - Lun, Shichun

AU - Guo, Haidan

AU - Adamson, John

AU - Cisar, Justin S.

AU - Davis, Tony D.

AU - Chavadi, Sivagami Sundaram

AU - Warren, J. David

AU - Quadri, Luis E.N.

AU - Tan, Derek S.

AU - Bishai, William R.

PY - 2013/10

Y1 - 2013/10

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AB - 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.

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

Abstract

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