Efficacy of DA-7218, a new oxazolidinone prodrug, in the treatment of experimental actinomycetoma produced by Nocardia brasiliensis

Molecules. 2008 Jan 11;13(1):31-40. doi: 10.3390/molecules13010031.

Abstract

Two recently synthesized oxazolidinones: (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-5-hydroxymethyloxazolidin-2-one (DA-7157) and its corresponding pro-drug (R)-3-(4-(2-(2-methyltetrazol-5-yl)-pyridin-5-yl)-3-fluorophenyl)-2-oxo-5-oxazolidinyl) methyl disodium phosphate (DA-7218), have shown very good activity against several Gram positive bacteria, including Nocardia and Mycobacterium. In the present work we evaluated the therapeutic in vivo effects of DA-7218 on Nocardia brasiliensis. We first determined the plasma concentration of the prodrug in BALB/c mice using several doses and then tested its activity in an in vivo experimental actinomycetoma murine model. At the end of treatment, there was a statistically significant difference between the three drug receiving groups (25, 12.5 and 5 mg/kg) and the control group(saline solution) (p=0.001), proving that DA-7218 is effective for the treatment of experimental murine actinomycetoma. This compound could be a potential option for patients affected with mycetoma by Nocardia brasiliensis.

MeSH terms

  • Acetamides / therapeutic use
  • Actinomycosis / drug therapy*
  • Actinomycosis / microbiology
  • Animals
  • Disease Models, Animal
  • Linezolid
  • Mice
  • Mice, Inbred BALB C
  • Mycetoma / drug therapy*
  • Mycetoma / microbiology
  • Nocardia / drug effects
  • Nocardia / physiology*
  • Nocardia Infections / drug therapy*
  • Nocardia Infections / microbiology
  • Organophosphates / blood
  • Organophosphates / pharmacology
  • Organophosphates / therapeutic use*
  • Oxazoles / blood
  • Oxazoles / pharmacology
  • Oxazoles / therapeutic use*
  • Oxazolidinones / pharmacology
  • Oxazolidinones / therapeutic use*
  • Prodrugs / pharmacology
  • Prodrugs / therapeutic use*
  • Tetrazoles / blood
  • Tetrazoles / pharmacology
  • Treatment Outcome

Substances

  • Acetamides
  • DA 7157
  • Organophosphates
  • Oxazoles
  • Oxazolidinones
  • Prodrugs
  • Tetrazoles
  • Linezolid
  • tedizolid phosphate