Resumo

P. brasiliensis is a dimorphic fungus ethiological agent of paracoccidioidomycosis, a systemic mycosis in Latin America.The usual therapeutic is with itraconazole and amphotericin B, which has high toxicity. The search for new antifungal promising prototypes is extremely important due the increase of the incidence of systemic mycosis. The maytenin molecule obtained from the Maytenus ilicifolia and the decyl gallate synthesized from gallic acid from Alchornea glandulosa, present several biological activities already described, like antifungal and antibacterial activities. These compounds were previously tested in our lab aganist Paracoccidioides complex strains, P. brasiliensis (S1, S2 e PS3) and P. lutzii (Pb01-like) species, according to the method proposed by CLSI (2002) document M-27-A2, presenting minnimun inhibitory concentration values under 0.12 mg/L Cytotoxity tests were also performed against lung cells (A549, MRC-5), oral keratinocytes (NOK) and metabolizing cells (HEPG2), where cell viability observed were above 70%. Proteins may be the main targets for drug design and by proteomic techniques is possible to identify the change in the expression of certain system, like when exposed to a certain compound. Thus, proteins differentially expressed in determined situations may show the effect on the proteome and therefore expose new targets through the action mechanisms exercised by contact with substances. Then proteomic investigations may include the identification of biomarkers in clinical research, the interaction analysis between the proteins, post translacional modifications, besides the identification of new targets in study of new drugs mechanisms. In this study, in order to identify protein differentially expressed in strains of Paracoccidioides complex, after treatment with maytenin and decyl gallate, 2-DE was performed, for the investigation and identification of new and seletive molecular targets for the development of new antifungal drugs, that have lower toxicity and broader spectrum of antifungal action for against several strains of this complex.