Resumo

The increasing incidence of drug-resistant pathogens and toxicity of existing antifungal compounds has drawn attention towards the new antimicrobial molecules activity. The search for new antifungal agents from plants may facilitate the treatment of major mycoses by reducing the adverse reactions. Systemic mycoses caused by yeasts are a worldwide problem. In Brazil, cryptococcosis and systemic candidiasis are the major opportunistic fungal diseases of immunocompromised patients especially those with AIDS. The aim of the present study was to evaluate the antifungal activity of the pure substance pedalitin, and protocatechuic acids derivates (pentyl, hexyl, octyl and nonyl) alone and in combination, with fluconazole (FCZ) and amphotericin B (AMB) against ATCC strains of Candida albicans, C. krusei, C. parapsilosis, C. glabrata, C. tropicalis, Cryptococcus neoformans, and C. neoformans isolates with susceptibility and resistance to fluconazole, and a bird isolate of C. gattii also resistant to fluconazole. The minimal inhibitory concentration (MIC) was determined by the broth dilution according to the broth microdilution method following the EUCAST (European Committee on Antimicrobial Susceptibility Testing) document EDef 7.1 (2008) with modifications. The antifungal action of both agents in combination was determined using the chessboard assay. The MIC values of the pedalitin and the protocatechuic acids derivates was between 0.97-31.25 mg/L against Candida and Cryptococcus species. When amphotericin B was combined with pedalitin, synergistic effect was found for C. krusei and C. neoformans. Synergistic activity was observed at various concentrations of protocatechuic acids combined with commercial drugs against Candida and Cryptococcus species, including resistant strains. C. krusei is naturally resistant to fluconazole and synergistic activity was found at concentrations of 8.0 mg/L for FCZ and 0.97 mg/L for the nonyl derivate. For the isolate of C. neoformans resistant to fluconazole, all derivatives of protocatechuic acid when combined with FCZ showed synergistic activity. The combination between pure substances from plants and antimicrobial drugs has been referred as a strategy for combating microbial development due to the production of an additive or synergistic effect.