title: In vitro and in vivo antileishmanial and trypanocidal studies of new N-benzene- and N-naphthalenesulfonamide derivatives.
abstract: We report in vivo and in vitro antileishmanial and trypanocidal activities of a new series of N-substituted benzene and naphthalenesulfonamides 1-15. Compounds 1-15 were screened in vitro against Leishmania infantum , Leishmania braziliensis , Leishmania guyanensis , Leishmania amazonensis , and Trypanosoma cruzi . Sulfonamides 6e, 10b, and 10d displayed remarkable activity and selectivity toward T. cruzi epimastigotes and amastigotes. 6e showed significant trypanocidal activity on parasitemia in a murine model of acute Chagas disease. Moreover, 6e, 8c, 9c, 12c, and 14d displayed interesting IC50 values against Leishmania spp promastigotes as well as L. amazonensis and L. infantum amastigotes. 9c showed excellent in vivo activity (up to 97% inhibition of the parasite growth) in a short-term treatment murine model for acute infection by L. infantum. In addition, the effect of compounds 9c and 14d on tubulin as potential target was assessed by confocal microscopy analysis applied to L. infantum promastigotes.
authors.affiliation: Departamento de Farmacia, Facultad de Ciencias de la Salud, Universidad CEU Cardenal Herrera , Edificio Seminario s/n, 46113-Moncada, Valencia, Spain.
authors.forename: Cristina
authors.initials: C
authors.lastname: Galiana-Roselló
authors.forename: Pablo
authors.initials: P
authors.lastname: Bilbao-Ramos
authors.forename: M Auxiliadora
authors.initials: MA
authors.lastname: Dea-Ayuela
authors.forename: Miriam
authors.initials: M
authors.lastname: Rolón
authors.forename: Celeste
authors.initials: C
authors.lastname: Vega
authors.forename: Francisco
authors.initials: F
authors.lastname: Bolás-Fernández
authors.forename: Enrique
authors.initials: E
authors.lastname: García-España
authors.forename: Jorge
authors.initials: J
authors.lastname: Alfonso
authors.forename: Cathia
authors.initials: C
authors.lastname: Coronel
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: González-Rosende
mesh_terms: D000818:Animals; D000981:Antiprotozoal Agents / Q000737:chemistry / Q000493:pharmacokinetics / Q000494:pharmacology / Q000633:toxicity; D001554:Benzene / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D002460:Cell Line; D003198:Computer Simulation; D015195:Drug Design; D005260:Female; D006801:Humans; D007891:Leishmania / Q000187:drug effects*; D051379:Mice; D013329:Structure-Activity Relationship; D013449:Sulfonamides / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D014349:Trypanosoma cruzi / Q000187:drug effects*
chemical_list: D000981:Antiprotozoal Agents; D013449:Sulfonamides; C051353:naphthalenesulfonamide; D001554:Benzene