Avaliação do efeito citototóxico, mutagênico e genotóxico do ácido xilópico, 16-hidroxi-caurano e ácido caurenóico e seus derivados e avaliação do efeito sinérgico com fluconazol frente à cepas de Candida parapsilosis

Abstract

Invasive candidiasis is a public health problem that affects hospitalized patients susceptible to infection. Among the species involved, Candida albicans is the most prevalent species according to epidemiological studies in Brazil and in the world, but in recent years non-albicans species are emerging. With the advent of new antifimgal drugs and indiscriminate use of them, some species are acquiring resistance to commonly used drugs such as fluconazole, making it necessary to search for new therapeutic strategies. The kaurenoic acid (KA) is a tetracyclic diterpene present in several plants known to exert various pharmacological activities such cytotoxic and antimicrobial actions in vitro. The aim of the study was to evaluate the antifungal potential of natural diterpenes kaurenoic acid (KA) , 16-hydroxy-kaurane (1) and xylopic acid (2) , and semi - synthetic derivatives of KA (3-5) against strains of Candida parapsilosis alone and in combination with fluconazole and evaluate the toxicity of these compounds. Four strains of Candida parapsilosis was used in our study. The broth microdilution method (M27 - S4) was used for antifungal susceptibility testing and cytotoxicity, genotoxicity and mutagenicity of molecules across the V79 mammalian cells by the MTT assay, micronucleus and comet respectively. It is concluded that compound four in combination with fluconazole, has activity against strains of fluconazole-resistant Candida parapsilosis and isn't citotoxic, genotoxic and mutagenic to v79 cell.