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] 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.

authors

Lun S,Guo H,Adamson J,Cisar JS,Davis TD,Chavadi SS,Warren JD,Quadri LE,Tan DS,Bishai WR

doi

10.1128/AAC.00918-13

subject

Has Abstract

pub_date

2013-10-01 00:00:00

pages

5138-40

issue

10

eissn

0066-4804

issn

1098-6596

pii

AAC.00918-13

journal_volume

57

pub_type

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