Synthesis and antitrypanosomal evaluation of E-isomers of 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives. Structure–activity relationships.

Departamento de Química Organica, Facultad de Química, Universidad de la República, CC 1157, 11800-Montevideo, Uruguay; Laboratorio de Química Orgánica, Facultad de Ciencias, Universidad de la República, Montevideo, Uruguay; Departamento de Fisicoquímica Biológica, Facultad de Ciencias, Universidad de la República, 11200-Montevideo, Uruguay; Departamento de Bioquímica, Facultad de Medicina, Universidad de la República, 11800-Montevideo, Uruguay; Bioenergetics Center, Universidad de Buenos Aires, Paraguay 2120, Buenos Aires, Argentina; Laboratorio de Química Cuántica, Facultad de Química, Universidad de la República, CC 1157, 11800-Montevideo, Uruguay; Departamento de Química Inorgánica y Analítica, Facultad de Ciencias Químicas y Farmacéuticas, Universidad de Chile, Santiago, Chile; Laboratorio de Patología Experimental, Facultad de Ciencias de la Salud, Universidad Nacional de Salta, Salta, Argentina
European Journal of Medicinal Chemistry (Impact Factor: 3.43). 04/2000; DOI: 10.1016/S0223-5234(00)00131-8

ABSTRACT Several novel semicarbazone derivatives were prepared from 5-nitro-2-furaldehyde or 5-nitrothiophene-2-carboxaldehyde and semicarbazides bearing a spermidine-mimetic moiety. All derivatives presented the E-configuration, as determined by NMR-NOE experiments. These compounds were tested in vitro as potential antitrypanosomal agents, and some of them, together with the parent compounds, 5-nitro-2-furaldehyde and 5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives, were also evaluated in vivo using infected mice. Structure–activity relationship studies were carried out using voltammetric response and lipophilic–hydrophilic balance as parameters. Two of the compounds (1 and 3) displayed the highest in vivo activity. A correlation was found between lipophilic–hydrophilic properties and trypanocidal activity, high RM values being associated with low in vivo effects.

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