Effects of piperonal nitro derivatives on candida species : antifungal activity against fluconazole - resistant strains is associated with oxidative DNA damage

Abstract

Recently, there has been a significant increase in invasive fungal infections, the treatment of which is limited to a quite small number of antifungal drugs. Natural products represent an important source of antifungal agents, mainly because of their natural coexistence with fungi present in each biome. Derivatives or semi-synthetic products can be used to optimize the pharmacological profile of natural products by modulating relevant biological properties. The present study evaluated the antifungal effect of piperonal nitro derivatives (PNDs) in Candida spp. strains resistant to fluconazole. The assessment of the antifungal effect was determined both by broth dilution and flow cytometry, as well as by the assessment of a potential mechanism of action of these compounds. All of the tested strains were susceptible to the tested compounds. Treatment with PNDs (1, 2 and 3) led to programmed cell death in Candida spp., probably because they play an antifungal role in specific DNA surrounding sites. In addition, ROS production was found to play a role in this process, observed as oxidative damage to DNA purine and pyrimidine bases. The PND compounds (1, 2 and 3) presented antifungal activity in vitro against strains of fluconazoleresistant Candida spp.