Sporotrichosis is the most frequent subcutaneous mycosis in the world and its increasing incidence has led to the
search for new therapeutic options for its treatment. In this study, we demonstrated that three structural analogues
of miltefosine (TCAN26, TC19, and TC70) showed inhibitory activity against
Sporothrix schenckii
sensu stricto
and that TCAN26 was more active in vitro than miltefosine against several isolates. Scanning electron microscopy
showed that
S. schenckii exposure to TCAN26 resulted in cells that were slightly more elongated than untreated cells.
Transmission electron microscopy showed that TCAN26 treatment induced loss of the regular cytoplasmic electrondensity
and altered the cell envelope (disruption of the cell membrane and cell wall, and increased cell wall thickness).
Additionally, TCAN26 concentrations required to kill
S. schenckii cells were lower than concentrations that
were cytotoxic in mammalian cells, and TCAN26 was more selective than miltefosine. Thus, the adamantylidene-substituted
alkylphosphocholine TCAN26 is a promising molecule for the development of novel antifungal compounds,
although further investigations are required to elucidate the mode of action of TCAN26 in
S. schenckii cells.
