Avaliação da atividade leishmanicida de 38 derivados chalcônicos (T1 - T51)
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Data
2014-01-27
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Universidade Estadual Paulista (Unesp)
Resumo
As leishmanioses atingem milhões de pessoas no mundo e são consideradas uma das Doenças Tropicais Negligenciadas (DTNs) por afetar, principalmente, as populações dos países em desenvolvimento. Há poucos fármacos disponíveis para o tratamento das leishmanioses, os quais são tóxicos e muitas vezes ineficazes devido ao surgimento de cepas resistentes; desta forma, a busca por novos compostos com atividade leishmanicida é justificada. Este trabalho iniciou-se com a triagem de 38 derivados chalcônicos, os quais foram avaliados quanto ao seu potencial leishmanicida e citotóxico. O derivado chalcônico T10 foi efetivo em ensaios utilizando formas promastigotas (IC50=3,4 μM) e em formas amastigotas intracelulares (IC50=4,7 μM), apresentando uma promissora atividade biológica e exibindo bom índice de seletividade (SI=41,0 μM). Portanto, este foi selecionado para realização de ensaios preliminares de análise de perfil proteico (eletroforese bidimensional) para fins de compreensão de mecanismo de ação do composto. Foi possível observar mudanças mais significativas na expressão de sete spots diferentes após tratamento com T10, os quais tiveram suas expressões aumentadas ou diminuídas quando comparados ao controle (sem tratamento).
Leishmaniasis affects millions of people worldwide and is considered one of Neglected Tropical Diseases (NTDs) by affecting mainly the populations in developing countries. There are few drugs available for the treatment of leishmaniasis, which are toxic and often ineffective due to the emergence of resistant strains, thus the search for new compounds with leishmanicidal activity is justified. This work was initiated with the screening of 38 chalcone derivatives, which were evaluated for their leishmanicidal and cytotoxic potential. The chalcone derivative T10 was effective in assays using promastigotes forms (IC50 = 3.4 μM) and against intracellular amastigotes forms (IC50 = 4.7 μM), showing a promising biological activity and exhibiting a good selectivity index (SI = 41.0 μM). Thus, this chalcone was selected to conduct preliminary tests of protein profile analysis (two-dimensional electrophoresis) to understand the mechanism of action of the compound. It was possible to observe more significant changes in the expression of seven different spots after treatment with T10, which had their expression increased or decreased compared to the control (no treatment).
Leishmaniasis affects millions of people worldwide and is considered one of Neglected Tropical Diseases (NTDs) by affecting mainly the populations in developing countries. There are few drugs available for the treatment of leishmaniasis, which are toxic and often ineffective due to the emergence of resistant strains, thus the search for new compounds with leishmanicidal activity is justified. This work was initiated with the screening of 38 chalcone derivatives, which were evaluated for their leishmanicidal and cytotoxic potential. The chalcone derivative T10 was effective in assays using promastigotes forms (IC50 = 3.4 μM) and against intracellular amastigotes forms (IC50 = 4.7 μM), showing a promising biological activity and exhibiting a good selectivity index (SI = 41.0 μM). Thus, this chalcone was selected to conduct preliminary tests of protein profile analysis (two-dimensional electrophoresis) to understand the mechanism of action of the compound. It was possible to observe more significant changes in the expression of seven different spots after treatment with T10, which had their expression increased or decreased compared to the control (no treatment).
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Bioquímica, Chalcona, Leishmania, Proteína