Submitted by Natalie Mendes (nataliermendes@gmail.com) on 2015-11-12T22:45:09Z No. of bitstreams: 1 Vers?o corrigida - vers?o final.pdf: 1423044 bytes, checksum: 6989a397b0d890ed1cb80eaaf86dcd52 (MD5) / Made available in DSpace on 2015-11-12T22:45:09Z (GMT). No. of bitstreams: 1 Vers?o corrigida - vers?o final.pdf: 1423044 bytes, checksum: 6989a397b0d890ed1cb80eaaf86dcd52 (MD5) Previous issue date: 2013-03-27 / Coordena??o de Aperfei?oamento de Pessoal de N?vel Superior - CAPES / 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. / Os f?rmacos nifurtimox e benzonidazol t?m sido utilizados no tratamento da doen?a de Chagas desde os anos 70. Ambos podem induzir efeitos colaterais nos pacientes e n?o possuem efic?cia na fase cr?nica. Portanto, se torna necess?ria a identifica??o de medicamentos mais eficientes e menos t?xicos para o tratamento desta doen?a. A s?ntese de complexos de metais de transi??o, especialmente o rut?nio, tem sido intensificada ao longo dos anos devido ao interesse nas aplica??es biol?gicas destes compostos. Este estudo teve, como objetivo, avaliar a atividade anti-Trypanosoma cruzi dos nitro/nitrosilo complexos de rut?nio, cis-[RuCl(NO2)(dppb)(5-me93bipy)] (1), cis-[Ru(NO2)2(dppb)(5-mebipy)] (2), ct-[RuCl(NO)(dppb)(5-mebipy)](PF6)2 (3) e cc-[RuCl(NO)(dppb)(5-mebipy)](PF6)2 (4). Foram avaliadas a citotoxicidade, a atividade anti-T. cruzi in vitro e in vivo e a inibi??o da atividade enzim?tica da cruza?na. Foi tamb?m avaliado o mecanismo de a??o do composto 3, o mais ativo dentre os demais. Os 4 compostos apresentaram baixa citotoxicidade e atividade tripanocida para as tr?s formas evolutivas do parasito. Apenas o composto 1 n?o inibiu a forma epimastigota. Em rela??o ? atividade enzim?tica, o composto 2 foi o ?nico que n?o inibiu a cruza?na. Em rela??o ao composto 3, os parasitos tratados com este composto apresentaram altera??es na membrana e presen?a de vac?olos correlacionados ?s marca??es positivas para iodeto de prop?dio e monodansilcadaverina, respectivamente. Al?m disso, o tratamento proporcionou redu??o de parasitemia e aumento de sobrevida dos camundongos infectados. Desta forma, os nitro/nitrosilo complexos de rut?nio representam uma classe de f?rmacos em potencial para o tratamento da doen?a de Chagas.