title: In vivo and in vitro anti-leishmanial activities of 4-nitro-N-pyrimidin- and N-pyrazin-2-ylbenzenesulfonamides, and N2-(4-nitrophenyl)-N1-propylglycinamide.
abstract: A series of compounds containing the nitrobenzene and sulfonamido moieties were synthesized and their leishmanicidal effect was assessed in vitro against Leishmaniainfantum promastigotes. Among the compounds evaluated, the p-nitrobenzenesulfonamides 4Aa and 4Ba, and the p-nitroaniline 5 showed significant activity with a good selectivity index. In a Balb/c mice model of L. Infantum, administration of compounds 4Aa, 4Ba or 5 (5mg/kg/day for 10 days, injected ip route) led to a clear-cut parasite burden reduction (ca. 99%). In an attempt to elucidate their mechanism of action, the DNA interaction of 4Aa and 5 was investigated by means of viscosity studies, thermal denaturation and nuclease activity assay. Both compounds showed nuclease activity in the presence of copper salt. The results suggest that compounds 4Aa, 4Ba and 5 represent possible candidates for drug development in the therapeutic control of leishmaniasis.
authors.affiliation: Department of Chemistry, University CEU Cardenal Herrera, 46113-Moncada, Valencia, Spain.
authors.forename: M Auxiliadora
authors.initials: MA
authors.lastname: Dea-Ayuela
authors.forename: Encarna
authors.initials: E
authors.lastname: Castillo
authors.forename: Marta
authors.initials: M
authors.lastname: Gonzalez-Alvarez
authors.forename: Celeste
authors.initials: C
authors.lastname: Vega
authors.forename: Miriam
authors.initials: M
authors.lastname: Rolón
authors.forename: Francisco
authors.initials: F
authors.lastname: Bolás-Fernández
authors.forename: Joaquín
authors.initials: J
authors.lastname: Borrás
authors.forename: M Eugenia
authors.initials: ME
authors.lastname: González-Rosende
mesh_terms: D000814:Aniline Compounds / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000818:Animals; D005998:Glycine / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology; D007896:Leishmaniasis / Q000188:drug therapy; D051379:Mice; D008807:Mice, Inbred BALB C; D011743:Pyrimidines / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D013449:Sulfonamides / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D014344:Trypanocidal Agents / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology; D000096926:Benzenesulfonamides
chemical_list: D000814:Aniline Compounds; D005998:Glycine; D011743:Pyrimidines; D013449:Sulfonamides; D014344:Trypanocidal Agents; D000096926:Benzenesulfonamides; C545769:N2-(4-nitrophenyl)-N1-propylglycinamide; C008625:nitroaniline