Efeito de dissulfetos de diarila sobre formas epimastigotas e tripomastigotas de Trypanosoma cruzi

• Ano de defesa: 2023
• Autor(a) principal: ANNY BEATRIZ DA SILVA
• Orientador(a): Alda Maria Teixeira Ferreira
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Fundação Universidade Federal de Mato Grosso do Sul
• País: Brasil
• Palavras-chave em Português: dissulfetos de diarila
• Link de acesso: https://repositorio.ufms.br/handle/123456789/5830

This work aims to evaluate the effect of synthetic compounds diaryl disulfides in replicative and infective forms of the etiological agent of Chagas Disease (CD), the protozoan Trypanosoma cruzi. CD is an endemic disease in Latin America, representing a serious public health problem, as it affects about 6 million people worldwide. In this perspective, the search for new compounds with anti-Trypanosoma activities that present low cytotoxicity and may represent an alternative for the treatment of this disease has been the objective of numerous research groups. There are reports in the literature of compounds of diaryl disulfides with antiproliferative activity against tumor cells, as well as action on protozoa. Therefore, this study proposes to evaluate the in vitro effect of Diaryl Disulfide compounds on the replicative and infective forms of T. cruzi. Biological assays of viability, growth, morphological analysis for epimastigotes and viability of trypomastigotes were carried out. The in silico analysis was also carried out to evaluate the ADMET properties of the compounds. During the analysis of the ADMET properties it was observed that the compounds present good absorption and do not present hepatotoxicity or mutagenicity. In the viability assay, it was observed that the compounds have biological activity on the epimastigotes forms of T. cruzi, with compounds D and E being the most active (3.124 and 5.091µM, respectively). The growth curve showed that from 24h of exposure, compound D caused a 50% inhibition and at 96h of exposure, this inhibition was 19.64%, demonstrating a reduction of activity according to the time of exposure. The recovery test was performed with compounds B, C and D showed that after 96h the inhibition values were between 26% and 40%, indicating a trypanostatic action. The morphological analysis performed with compounds B and D indicated that these compounds cause morphological changes that affect the viability of the parasite. The viability assay with trypomastigotes treated with compound D indicated that the compound has action on the infective form of the parasite, with an IC50 of 10.90 µM. Keywords: Diaryl Disulfides, Trypanosoma cruzi, Chagas Disease.