Avaliação da atividade anti-Trypanosoma cruzi de nitrosilo/nitro complexos de rutênio em modelos experimentais in vitro e in vivo

• Ano de defesa: 2013
• Autor(a) principal: Bastos, Tanira Matutino
• Orientador(a): Soares, Milena Botelho Pereira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Estadual de Feira de Santana
• Programa de Pós-Graduação: Mestrado Acadêmico em Biotecnologia
• Departamento: DEPARTAMENTO DE CIÊNCIAS BIOLÓGICAS
• País: Brasil
• Palavras-chave em Português: Doença de Chagas; Complexo de rutênio; Óxido nítrico; Atividade tripanocida; Autofagia
• Palavras-chave em Inglês: Chagas’ disease; Ruthenium complex; Nitric oxide; Trypanocidal activity; Autophagy
• Área do conhecimento CNPq: CIENCIAS BIOLOGICAS
• Link de acesso: http://localhost:8080/tede/handle/tede/259

Nifurtimox and benznidazole have been used to treat Chagas’ disease since the 70s. Both drugs can induce side effects on the patients and are not effective when given during the chronic phase. Therefore, more efficient drugs with lower toxicity are needed for the treatment of this disease. The synthesis of complexes of transition metals, especially ruthenium has been increased over the years due to the interest in the biological applications of these compounds. The present study aimed to evaluate the activity of anti-Trypanosoma cruzi of nitro/nitrosyl ruthenium complexes, cis-[RuCl(NO2)(dppb)(5-mebipy)] (1), cis-[Ru(NO2)2(dppb)(5-mebipy)] (2), ct-[RuCl(NO)(dppb)(5-mebipy)](PF6)2 (3) and cc-[RuCl(NO)(dppb)(5-mebipy)](PF6)2 (4). We evaluated the cytotoxicity, anti-T. cruzi activity in vitro and in vivo, and inhibition of cruzain enzyme activity. We also evaluated the mechanism of action of compound 3, the most active among the others. All compounds showed low cytotoxicity and trypanocidal activity against the three evolutionary forms of the parasite. Only compound 1 did not inhibit the epimastigote form. Regarding the enzymatic activity, compound 2 was the only one who did not inhibit the cruzain activity. Treatment with compound 3 caused changes in the membrane and vacuoles of the parasites, correlated to positive stains for propidium iodide and monodansylcadaverine, respectively. Moreover, the treatment with compound 3 caused a reduction of parasitemia and increased survival of infected mice. Thus, the nitro/nitrosyl ruthenium complexes represent a potential class of drugs for the treatment of Chagas' disease.