Article

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: 3.35). 04/2000; DOI:10.1016/S0223-5234(00)00131-8 pp.343-350

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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    Article: Screening of Potential anti-Trypanosoma cruzi Candidates: In Vitro and In Vivo Studies.
    Maria de Nazaré C Soeiro, Solange Lisboa de Castro
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    ABSTRACT: Chagas disease (CD), caused by the intracellular protozoan Trypanosoma cruzi, is a parasitic illness endemic in Latin America. In the centennial after CD discovery by Carlos Chagas (1909), although it still represents an important public health problem in these affected areas, the existing chemotherapy, based on benznidazole and nifurtimox (both introduced more than four decades ago), is far from being considered ideal due to substantial toxicity, variable effect on different parasite stocks and well-known poor activity on the chronic phase. CD is considered one of the major "neglected" diseases of the world, as commercial incentives are very limited to guarantee investments for developing and discovering novel drugs. In this context, our group has been pursuing, over the last years, the efficacy, selectivity, toxicity, cellular targets and mechanisms of action of new potential anti-T. cruzi candidates screened from an in-house compound library of different research groups in the area of medicinal chemistry. A brief review regarding these studies will be discussed, mainly related to the effect on T. cruzi of (i) diamidines and related compounds, (ii) natural naphthoquinone derivatives, and (iii) megazol derivatives.
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Keywords

5-nitrothiophene-2-carboxaldehyde semicarbazone derivatives
 
highest
 
lipophilic–hydrophilic properties
 
mice
 
NMR-NOE experiments
 
novel semicarbazone derivatives
 
potential antitrypanosomal agents
 
semicarbazides bearing
 
Structure–activity relationship studies
 
trypanocidal activity
 
vivo activity
 
vivo effects
 
voltammetric response