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

• Published in: Journal of the Brazilian Chemical Society Vol. 16; no. 4; pp. 774 - 782
• Main Authors: La-Scalea, Mauro Aquiles, Menezes, Carla Maria de Souza, Julião, Murilo Sérgio da Silva, Chung, Man Chin, Serrano, Sílvia Helena Pires, Ferreira, Elizabeth Igne
• Format: Journal Article
• Language: English
• Published: Sociedade Brasileira de Química 01-08-2005
• Subjects: CHEMISTRY, MULTIDISCIPLINARY; nitrofurazone prodrug; nitro-radical anion; nitrofurazone; cyclic voltammetry; hydroxymethylnitrofurazone
• ISSN: 0103-5053; 1678-4790
• DOI: 10.1590/S0103-50532005000500015

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.