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

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.

• Authors: Nelly Alejandra Espinoza-González, Oliverio Welsh, Noemi Waksman de Torres, Norma Cavazos-Rocha, Jorge Ocampo-Candiani, Salvador Said-Fernandez, Gerardo Lozano-Garza, Sung-Hak Choi, Lucio Vera-Cabrera
• Journal: Molecules (Basel, Switzerland) (Molecules) Vol. 13 Issue 1 Pg. 31-40 (Jan 11 2008) ISSN: 1420-3049 [Electronic] Switzerland
• PMID: 18259127 (Publication Type: Journal Article)

Chemical References

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

Topics

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