Investiga??o da atividade antileishmania in vitro de chalconas-tiossemicarbazonas

• Ano de defesa: 2019
• Autor(a) principal: Mendes, Edin?a Pastro
• Orientador(a): Echevarria, Aurea
• Banca de defesa: Echevarria, Aurea, Santos, Eduardo Caio Torres dos, Santos, Fernanda Nunes, Silva, Lucia Helena Pinto da, Coelho, Irene da Silva
• Tipo de documento: Tese
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal Rural do Rio de Janeiro
• Programa de Pós-Graduação: Programa de P?s-Gradua??o em Ci?ncia, Tecnologia e Inova??o em Agropecu?ria
• Departamento: Pr?-Reitoria de Pesquisa e P?s-Gradua??o
• País: Brasil
• Palavras-chave em Português: Leishmanioses; Chalconas; Tiossemicarbazonas
• Palavras-chave em Inglês: Leishmaniosis; Chalcones; Thiosemicarbazones
• Área do conhecimento CNPq: Bioqu?mica; Parasitologia
• Link de acesso: https://tede.ufrrj.br/jspui/handle/jspui/5651

The leishmaniosis are a serious global public health problem, affecting patients with pronounced deformity, morbidity and mortality, as well as difficulty of access and adherence to treatment, lack of investment in the development of new drugs by pharmaceutical industry and inefficient social policies. The treatment used is not adequate due to drug effectiveness and toxicity. Additionally, resistance to available drugs has been shown by the sensitivity of several strains to these substances and treatment can be long and require hospitalization. In an attempt to find new anti-parasitic agents that can help with Leishmaniosis treatment, a series of seven chalcones-thiosemicarbazones with different substituents (CT-H, CT-Me, CT-CN, CT-F, CT-Br, CT-Cl and CT-NO2) against the promastigote forms of parasites of Leishmania spp was assessed. Evaluation started through the screening of different substances at 50?M concentration with promastigote forms of L. amazonensis, and when leishmanicidal activity was observed, a further evaluation with L. amazonensis, L. infantum and L. braziliensis was performed in the form of promastigotes at concentration range of 50 to 1.56 ?M dissolved in DMSO. Parasite cultures were prepared with Schneider?s medium supplemented with 10% or 20% of bovine fetal serum, arranged in 96 wells microplates and incubated at 26? C for 12 h. All trials were conducted in triplicate in three independent assays and pentamidine was used as positive control. The cytotoxicity of these compounds was assessed in uninfected cells with murine peritoneal macrophages in 24 h presenting LD50 values (?M) for CT-Br and CT-Cl 44.24 and 32.75 ?M respectively, demonstrating that those compounds are less cytotoxic than pentamidine whose value was = 8.5 . The promastigate forms were cultivated with and without these substances in Schneider?s culture medium and incubated at the 26? C for 12 hours using pentamidine isethionate as a reference drug. After incubation, the viability of the parasites was determined by using the MTT assay. The results showed that the CT-Cl was the most active compound for the three species tested, presenting IC50 = 5.22 ?M to L. amazonensis, 3.97 ?M to L. infantum and 3.89 ?M to L. braziliensis, respectively. Pentamidine presented IC50 = 5.20 ?M. The other compounds also obtained good results with IC50 in the range of 4.34 to 14.80 ?M. In trials of CT with the L. amazonensis axenic amastigotes IC50 values were obtained in the range of 6.18 to 14.74 ?M, indicating very interesting activity. This study also investigated the mechanism of action of most active substances in trypanothione reductase enzyme and the NO synthase pathways by evaluating nitric oxide. However, positive results were not observed to support those pathways as significant to chalcones-thiosemicarbazones action. The results obtained by the evaluation of chalcones-thiosemicarbazones action on the three species indicate this class of substances as potential antileishmanial agents.