XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:76-1

Poster (Painel)

76-1

The natural product argentilactone as a candidate anti-P. brasiliensis

Authors:

Renata Vilar (UFG - Universidade Federal de GoiásICB - Instituto de Ciências Biológicas) ; Ricardo Justino Alves (UFG - Universidade Federal de GoiásIQ - Instituto de Química) ; Cecilia Maria de Oliveira (UFG - Universidade Federal de GoiásIQ - Instituto de Química) ; Cirano José Ulhoa (UFG - Universidade Federal de GoiásICB - Instituto de Ciências Biológicas) ; Alexandre Melo Bailão (UFG - Universidade Federal de GoiásICB - Instituto de Ciências Biológicas) ; Célia Maria Almeida Soares (UFG - Universidade Federal de GoiásICB - Instituto de Ciências Biológicas) ; Maristela Pereira (UFG - Universidade Federal de GoiásICB - Instituto de Ciências Biológicas)

Abstract

The dimorphic fungus Paracoccidioides brasiliensis is the ethiological agent of paracoccidioidomycosis, a deep mycosis of high incidence in Latin America. The toxicity of drugs and the appearance of resistant strains have imposition the search for new therapeutic approaches. Here we verified the acting of argentilactone from H. ovalifolia, and its analogues, against P. brasiliensis. The results showed an inhibition dose dependent of argentilactone under P. brasiliensis yeast cells. The inhibition of growth was higher in the presence of acetate (MIC=9 μg/mL) than glucose (MIC=18 μg/mL). Similar results were found to reduced argentilactone. A small effect was observed to epoxy argentilactone and diol argentilactone. We evaluate if argentilactone and analogous interfere in the dimorphic transition of P. brasiliensis. The results indicated inhibition dose dependent of argentilactone under the dimorphism of P. brasiliensis. The inhibition of dimorphism was higher in the presence of acetate than glucose. Although the effect has been less, similar results were found to reduced argentilactone. The analogous epoxy argentilactone and diol argentilactone do not interfered on dimorphism process. We also investigated if argentilactone and analogues interfere on native PbICL. Argentilactone and reduced argentilactone inhibited PbICL activity. The higher inhibition was observed in the presence of acetate (IC50=50 μM), condition which the enzyme is more active, than glucose (IC50=80 μM). None inhibition could be observed to epoxy argentilactone or diol argentilactone. The inhibition of argentilactone and analogues was also investigated to recombinant PbICL. The inhibition was higher in the presence of argentilactone (IC50=28.8 μM) than reduced argentilactone (IC50=30.2 μM). On the other hand, epoxy argentilactone and diol argentilactone were inactive against recombinant PbICL. The kinetic parameters Km and Vmáx obtained in the presence of argentilactone and reduced argentilactone indicated a mixed type inhibition. We are investigating the mechanism of action of argentilactone by proteomic analysis.਀ ਀䘀椀渀愀渀挀椀愀氀猀甀瀀瀀漀爀琀㨀䌀一倀焀Ⰰ 䌀䄀倀䔀匀Ⰰ 䘀䤀一䔀倀Ⰰ 䘀䄀倀䔀䜀

Keyword: Paracoccidioides brasiliensis, Hyptis ovalifolia, argentilactone, inhibition, isocitrate lyase

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