Obtenção e caracterização de pró-fármacos derivados de terpenos de origem vegetal com potencial atividade antichagásica

• Ano de defesa: 2017
• Autor(a) principal: Freitas, Marcelo da Silva [UNIFESP]
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de São Paulo
• Palavras-chave em Português: Trypanossoma cruzi; Leishmania; Neglected diseases; Nitro-thiosemicarbazones; Terpenes; Doenças negligenciadas; Nitro-tiossemicarbazonas; Terpenos
• Link de acesso: https://sucupira.capes.gov.br/sucupira/public/consultas/coleta/trabalhoConclusao/viewTrabalhoConclusao.jsf?popup=true&id_trabalho=5635129; https://repositorio.unifesp.br/handle/11600/50441

Current chemotherapy alternative directed to the treatment of Leishmaniasis and Chagas disease shows to be inadequate because the existence of parasitic resistance to treatment, limited efficacy to certain stages of the disease and high toxicity. The context that keeps similarities between the diseases is its origin in flagellate protozoan, Trypanosoma cruzi, and Leishmania spp, and its inclusion into the list of those diseases considered neglected by OMS. The populations under risk in endemic regions, its global spread, and the severe impact on infected people, make necessary the development of new compounds which promote safe and effective treatment that contributed for the reduction of the incidence of those diseases, once the low interest of pharmaceutical industries still persist. This work proposed the synthesis and characterization of a series of prodrugs obtained by binding an inhibitor of cysteine protease cruzain, and natural terpene compounds which have already exhibited antileishimanial and antichagasic activities already described, in order to minimize the toxicity of both groups, as well preventing the emergence of parasitic resistance by acting through two distinct biochemical pathways. The compounds were obtained by carbamate synthesis, using 4-nitrophenylchloroformate as a coupling agent, to link the terpene moiety to the cruzain inhibitor. The characterization was carried out by infrared and NMR analysis, and the compounds were subjected to in vitro assays for determining cytotoxicity to mammalian cells and antiprotozoal activity.