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] 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.affiliation: Center for Tuberculosis Research, Johns Hopkins University School of Medicine, Baltimore, Maryland, USA.
authors.forename: Shichun
authors.initials: S
authors.lastname: Lun
authors.forename: Haidan
authors.initials: H
authors.lastname: Guo
authors.forename: John
authors.initials: J
authors.lastname: Adamson
authors.forename: Justin S
authors.initials: JS
authors.lastname: Cisar
authors.forename: Tony D
authors.initials: TD
authors.lastname: Davis
authors.forename: Sivagami Sundaram
authors.initials: SS
authors.lastname: Chavadi
authors.forename: J David
authors.initials: JD
authors.lastname: Warren
authors.forename: Luis E N
authors.initials: LE
authors.lastname: Quadri
authors.forename: Derek S
authors.initials: DS
authors.lastname: Tan
authors.forename: William R
authors.initials: WR
authors.lastname: Bishai
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D005260:Female; D008168:Lung / Q000187:drug effects* / Q000378:metabolism / Q000382:microbiology; D051379:Mice; D008807:Mice, Inbred BALB C; D009169:Mycobacterium tuberculosis / Q000187:drug effects*; D010080:Oxazoles / Q000378:metabolism*; D011897:Random Allocation
chemical_list: D000900:Anti-Bacterial Agents; D010080:Oxazoles; C018608:mycobactins