Voltammetric behavior of nitrofurazone and its hydroxymethyl prodrug with potential anti-Chagas activity

Autor(es)

Mauro Aquiles La-Scalea ^[1] ; Carla Maria de Souza Menezes ^[2] ; Murilo Sérgio da Silva Julião ; Man Chin Chung ^[4] ; Sílvia Helena Pires Serrano ^[5] ; Elizabeth Igne Ferreira ^[6]

Afiliação do(s) autor(es)

^[1] Universidade de São Paulo (USP). Faculdade de Ciências Farmacêuticas - Brasil

^[2] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas - Brasil

^[4] Universidade Estadual Paulista. Faculdade de Ciências Farmacêuticas - Brasil

^[5] Universidade de São Paulo. Instituto de Química - Brasil

^[6] Universidade de São Paulo. Faculdade de Ciências Farmacêuticas - Brasil

• Tipo de documento: Artigo Científico
• Fonte: Journal of the Brazilian Chemical Society; v. 16, n. 4, p. 774-782, 2005-08-00.
• Área do conhecimento: Ciências da Saúde - Farmácia
• Notas: O artigo consta como produto de três processos: 01/01192-3 em nome de Elizabeth Igne Ferreira; 01/09418-0 e 03/10763-0 em nome de Mauro Aquiles La Scalea
• Assunto(s): Anti-infecciosos Nitrofurazona Doença de Chagas Trypanosoma cruzi

Resumo

Chagas' disease is a serious health problem for Latin America. The situation is worsened by the lack of efficient chemotherapy. The two available commercial drugs, benznidazole and nifurtimox, are more effective in the acute phase of the disease. Nitrofurazone is active against Trypanosoma cruzi, however its high toxicity precludes its current use in parasitosis. Hydroxymethylnitrofurazone is a prodrug of nitrofurazone. It is more active against Trypanosoma cruzi than nitrofurazone, besides being less toxic. This work shows the voltammetric behavior of nitrofurazone and a comparison with those of metronidazole and chloramphenicol using cyclic, linear sweep and differential pulse voltammetries. For these drugs also the prediction of the diffusion coefficients using Wilke-Chang equation was performed. The reduction of nitrofurazone is pH-dependent and in acidic medium the hydroxylamine derivative, involving four electrons, is the principal product formed. In aqueous-alkaline medium and with a glassy carbon electrode pre-treatment the reduction of nitrofurazone occurs in two steps, the first involving one electron to form the nitro-radical anion and the second corresponding to the hydroxylamine derivative formation. Hydroxymethylnitrofurazone presented the same voltammetric behavior and electroactivity, indicating that the molecular modification performed in nitrofurazone did not change its capacity to be reduced. A brief discussion regarding the differences in biological activity between the two compounds is also presented. (AU)

• Processo FAPESP: 01/01192-3 - Antichagásicos potenciais derivados de compostos nitro-heterocíclicos
• Beneficiário: Elizabeth Igne Ferreira
• Modalidade de apoio: Auxílio à Pesquisa - Temático
• Processo FAPESP: 03/10763-0 - Estudos de compostos nitro-heterocíclicos potencialmente antichagásicos
• Beneficiário: Mauro Aquiles La Scalea
• Modalidade de apoio: Auxílio à Pesquisa - Programa Primeiros Projetos