title: 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.affiliation: Servicio de Dermatología, Hospital Universitario Dr. José E. González, Ave. Madero y Gonzalitos S/N Col. Mitras Centro Monterrey, N.L. México.
authors.forename: Nelly Alejandra
authors.initials: NA
authors.lastname: Espinoza-González
authors.forename: Oliverio
authors.initials: O
authors.lastname: Welsh
authors.forename: Noemi Waksman
authors.initials: NW
authors.lastname: de Torres
authors.forename: Norma
authors.initials: N
authors.lastname: Cavazos-Rocha
authors.forename: Jorge
authors.initials: J
authors.lastname: Ocampo-Candiani
authors.forename: Salvador
authors.initials: S
authors.lastname: Said-Fernandez
authors.forename: Gerardo
authors.initials: G
authors.lastname: Lozano-Garza
authors.forename: Sung-Hak
authors.initials: SH
authors.lastname: Choi
authors.forename: Lucio
authors.initials: L
authors.lastname: Vera-Cabrera
mesh_terms: D000081:Acetamides / Q000627:therapeutic use; D000196:Actinomycosis / Q000188:drug therapy* / Q000382:microbiology; D000818:Animals; D004195:Disease Models, Animal; D000069349:Linezolid; D051379:Mice; D008807:Mice, Inbred BALB C; D008271:Mycetoma / Q000188:drug therapy* / Q000382:microbiology; D009615:Nocardia / Q000187:drug effects / Q000502:physiology*; D009617:Nocardia Infections / Q000188:drug therapy* / Q000382:microbiology; D010755:Organophosphates / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D010080:Oxazoles / Q000097:blood / Q000494:pharmacology / Q000627:therapeutic use*; D023303:Oxazolidinones / Q000494:pharmacology / Q000627:therapeutic use*; D011355:Prodrugs / Q000494:pharmacology / Q000627:therapeutic use*; D013777:Tetrazoles / Q000097:blood / Q000494:pharmacology; D016896:Treatment Outcome
chemical_list: D000081:Acetamides; C515039:DA 7157; D010755:Organophosphates; D010080:Oxazoles; D023303:Oxazolidinones; D011355:Prodrugs; D013777:Tetrazoles; D000069349:Linezolid; C515040:tedizolid phosphate