Inibição da isocitrato liase de Paracoccidioides brasiliensis pelo produto natural argentilactona

• Ano de defesa: 2010
• Autor(a) principal: PRADO, Renata Silva do
• Orientador(a): PEREIRA, Maristela
• Tipo de documento: Dissertação
• Tipo de acesso: Acesso aberto
• Idioma: por
• Instituição de defesa: Universidade Federal de Goiás
• Programa de Pós-Graduação: Mestrado em Biologia
• Departamento: Ciências Biolóicas
• País: BR
• Palavras-chave em Português: Isocitrato liase; Paracoccidioides brasiliensis; inibição; Hyptis ovalifolia; 1.Paracoccidioides brasiliensis 2.Isocitrato Liase 3.Argentilactona
• Palavras-chave em Inglês: Isocitrate lyase; Paracoccidioides brasiliensis; Inhibitory activity; Hyptis ovalifolia
• Área do conhecimento CNPq: CNPQ::CIENCIAS BIOLOGICAS::BIOQUIMICA::BIOLOGIA MOLECULAR
• Link de acesso: http://repositorio.bc.ufg.br/tede/handle/tde/1252

The fungus Paracoccidioides brasiliensis is the causative agent of paracoccidioidomicosys (PCM), the most prevalent human systemic mycosis in Latin America. The toxicity of drugs and the appearance of resistant strains have imposition the search for new therapeutic approaches. Plants with reputed antimicrobial uses represent a rich source for the screening of potential antifungal compounds. In this work, we investigated the inhibitory action of argentilactone, extracted from the essential oil of Hyptis ovalifolia, and its analogues on P. brasiliensis yeast cells, during the differentiation from mycelium to yeast, on native and recombinant PbICL. Sensitivity tests on plates, which assessed the activity of argentilactone on yeast cells of P. brasiliensis showed both argentilactone as reduced argentilactone interfered in fungus growth, affecting the cells in a dose-dependent way. The experiments evaluating the minimum inhibitory concentration (MIC), which evaluated the influence of the compounds during the transition from mycelium to yeast in P. brasiliensis showed that argentilactone and reduced argentilactone interferes in this process, also in a dose-dependent way. A specific activity of isocitrate lyase of the fungus, both recombinant as native, as measured by tests of enzyme activity was also affected by the compounds. The type of inhibition promoted by argentilactone and reduced argentilactone was defined as inhibition of mixed type through tests of enzyme kinetics. Different carbon sources (acetate and glucose) have directly influence on the processs of inhibition. The analogues epoxy argentilactone and diol argentilactone not inhibit the growth and differentiation of P. brasiliensis. In addition, it not inhibited the enzyme isocitrate lyase native or recombinant.