A Cyclam Salt as an Antifungal Agent: Interference with ICandida/I spp. and ICryptococcus neoformans/I Mechanisms of Virulence

The importance of fungal infections, particularly those caused by yeasts, is increasing among the medical community. Candida albicans and Cryptococcus neoformans are amongst the high-priority fungal species identified by the World Health Organization (WHO) and are considered in the critical group, while Candida krusei is included in the medium-priority group. The cyclam salt H[sub.4][H[sub.2]([sup.4-CF3]PhCH[sub.2])[sub.2]Cyclam]Cl[sub.4] proved to be active against the growth of these three yeasts, and the aim of this work was to verify its interference with their virulence mechanisms, whether shared or unique. H[sub.4][H[sub.2]([sup.4-CF3]PhCH[sub.2])[sub.2]Cyclam]Cl[sub.4] significantly inhibited biofilm production and catalase activity, being able to interfere with C. albicans dimorphic transition and C. neoformans melanin production. At the minimal inhibitory concentration (MIC) values, H[sub.4][H[sub.2]([sup.4-CF3]PhCH[sub.2])[sub.2]Cyclam]Cl[sub.4] had no antioxidant effect, as determined by the DPPH method. When using the RAW264.7 macrophage cell line, H[sub.4][H[sub.2]([sup.4-CF3]PhCH[sub.2])[sub.2]Cyclam]Cl[sub.4] reduced nitric oxide (NO) detection (the Griess reaction), but this effect was associated with a significant toxic effect on the cells.