XI International Meeting on Paracoccidioidomycosis

XI International Meeting on Paracoccidioidomycosis

Resume:42-1

Poster (Painel)

42-1

CAMPHENE THIOSEMICARBAZIDE AND ITS THIOSEMICARBAZONES DERIVATIVES INHIBIT ISOCITRATE LYASE ACTIVITY AND Paracoccidioides brasiliensis GROWTH

Authors:

Symone Vitoriano da Conceição Castro (UFG - Universidade Federal de Goiás) ; Renata Silva do Prado Vilar (UFG - Universidade Federal de Goiás) ; Karine Martins de Oliveira (UFG - Universidade Federal de Goiás) ; Cecília Maria Alves de Oliveira (UFG - Universidade Federal de Goiás) ; Ludmila Bringel Pires (UFG - Universidade Federal de Goiás) ; Célia Maria de Almeida Soares (UFG - Universidade Federal de Goiás) ; Maristela Pereira (UFG - Universidade Federal de Goiás)

Abstract

The fungus Paracoccidioides brasiliensis is the etiological agent of paracoccidioidomycosis (PCM), a systemic mycosis of great interest to Latin America countries. The PCM is an important public health problem due to its high disabling potential and the amount of premature deaths it causes. Treatment of PCM, as well as other fungal infections, is protracted, lasting months to years, with serious adverse effects and providing no effective cure, so it is common to abandonment of treatment by patients. Although the treatment options are considered potent, keep emerging isolates resistant or multidrug-resistant, even when used in combination therapies. Thus, the research and development of new therapeutic approaches are of great importance. Here we verified if thiosemicarbazide deriving from monoterpene camphene and its thiosemicarbazones derivatives obtained by synthesis chemistry could inhibit the fungal growth. In addition, it was investigated if those compounds could inhibit the recombinant enzymes isocitrate lyase (PbICL) and malate synthase (PbMLS) of P. brasiliensis, key enzymes of the glyoxylate cycle and essential to the some fungus survive in the host environment. The test made in microplate aimed to assess the influence of the compounds on yeast cells of the fungus allowing the determination of IC50. The stock solutions were prepared in dimethylsulfoxide (DMSO) and water, from which dilutions were prepared and the concentration of the compounds were 9-72 &mug/ml. The culture was incubated at 37Â°C for a period of 7 days and daily readings were performed in microplate reader to determine cell growth. The results showed a dose dependent inhibition of camphene thiosemicarbazide and some of its thiosemicarbazones derivatives under P. brasiliensis yeast cells. The inhibition of PbICL was also evaluated by using microplate with different concentrations (10-40 &muM) of the compounds tested. The results showed that some derivatives from thiosemicarbazide inhibited PbICL activity. So, we evaluate if those derivatives also interfere in the activity of PbMLS. The results showed that the derivatives tested did not inhibit the activity of PbMLS indicating the selectivity of the compounds to PbICL.਀ Financial Support: CAPES, CNPq, FINEP, FAPEG, IFS.

Keyword: inhibition, isocitrate lyase, malate synthase, Paracoccidioides brasiliensis, thiosemicarbazide

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