Efficacy of DA-7218, a New Oxazolidinone Prodrug, in the Treatment of Experimental Actinomycetoma Produced by Nocardia brasiliensis.docVIP

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Efficacy of DA-7218, a New Oxazolidinone Prodrug, in the Treatment of Experimental Actinomycetoma Produced by Nocardia brasiliensis.doc

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Efficacy of DA-7218, a New Oxazolidinone Prodrug, in the Treatment of Experimental Actinomycetoma Produced by Nocardia brasiliensis

Molecules 2008, 13, 31-40 molecules ISSN 1420-3049 ? 2008 by MDPI /molecules Full Paper Efficacy of DA-7218, a New Oxazolidinone Prodrug, in the Treatment of Experimental Actinomycetoma Produced by Nocardia brasiliensis Nelly Alejandra Espinoza-González 1, Oliverio Welsh 1, Noemi Waksman de Torres 2, Norma Cavazos-Rocha2, Jorge Ocampo-Candiani1, Salvador Said-Fernandez 3, Gerardo Lozano-Garza3, Sung-Hak Choi 4 and Lucio Vera-Cabrera 1,* 1 Servicio de Dermatología, Hospital Universitario “Dr. José E. González” Ave. Madero y Gonzalitos S/N Col. Mitras Centro Monterrey, N.L. México 64460; E-mail: nelly.espinoza@ 2 Departamento de Química Analítica, Facultad de Medicina, Universidad Autónoma de Nuevo León, Ave. Madero y Dr. Eduardo Aguirre Peque?o S/N, Col Mitras Centro, Monterrey, N.L., México 64460 3 Centro de Investigación Biomédica del Noreste (CIBIN) del IMSS, 2 de Abril y San Luis Potosí, Col. Independencia, Monterrey, N.L., México 64720 4 Research Laboratory, Dong-A Pharmaceutical Co., Ltd., Yongin, and College of Pharmacy, Sungkyunkwan University, Suwon, South Korea * Author to whom correspondence should be addressed: E-mail: luvera_99@ Received: 2 November 2007; in revised form: 29 December 2007 / Accepted: 29 December 2007 / Published: 11 January 2008 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 actinomy