POTENCIAL ATIVIDADE DOS FÁRMACOS OXICONAZOL E LANSOPRAZOL SOBRE FORMAS TRIPOMASTIGOTAS DE Trypanosoma cruzi Dm28c

• Ano de defesa: 2024
• Autor(a) principal: DANIEL CAMILO FONSECA CAVALCANTI
• 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: Doença de Chagas; In silico; Kinetoplastida; Metaciclogênese; Reposicionamento de fármacos
• Link de acesso: https://repositorio.ufms.br/handle/123456789/9067

Chagas disease is caused by the protozoan Trypanosoma cruzi. It is classified as a neglected tropical disease and is endemic in Latin America, where up to 7 million people are believed to be infected. The available treatments for this disease are not very effective in the chronic phase and also have adverse effects. The process of discovering new drugs is long and expensive, so drug repositioning strategies are gaining ground as they can reduce costs and time to market. The aim of this study was to evaluate the activity of two drugs, previously selected in silico, on metacyclic trypomastigotes of T. cruzi Dm28c. Cytotoxicity tests were performed with the drugs oxiconazole (OXI) and lansoprazole (LZP) against Vero cells and metacyclic trypomastigote forms obtained in vitro, under chemically defined conditions, with the aim of determining the concentration capable of inhibiting 50% of parasite viability. Subsequently, tests were performed to evaluate the influence of the drugs on the process of metacyclogenesis in vitro. Using the CC50 (50% cytotoxic concentration) and IC50 (50% inhibitory concentration) data, the SI (selectivity index) was calculated. OXI showed a cytotoxic effect with a CC50 of 45.11 μM, in contrast to LZP which showed no cytotoxicity. OXI had an effect on trypomastigote forms with an IC50 of 279.6 μM and an IS of 0.16, while LZP had an IS of 2.46 and less activity against the parasite. Both drugs had an effect on the differentiation process, where intermediate forms were more abundant than metacyclic trypomastigotes, indicating that the drugs affected the process from the onset of differentiation, preventing or delaying its completion. Thus, both drugs had an effect during metacyclogenesis, but only OXI acted against the metacyclic trypomastigote forms.