Abstract. A new azasterol 22-hydrazine-imidazolin-2-yl-chol-5-ene-3β-ol (AH3) and their derivatives [Au(AH3)Cl] (1) and [Cu(AH3)2(H2O)2](NO3)2 (2) were synthesized and characterized by a combination of elemental analyses, 1H and 13C -NMR, UV-vis and infrared spectroscopies. The interactions with two targets DNA and TrxR were investigated. The results from these studies suggested that these metal-azasterol complexes interact with DNA most probably by covalent binding. Complex 1 showed also the ability to strongly inhibit TrxR. Additionally, their activities against yeast cells of Sporothrix spp. were evaluated; finding that complex 1 was the most active, even better than itraconazole.

Resumen. Un nuevo azasterol 22-hidrazina-imidazolin-2-il-col-5-en-3β-ol (AH3) y sus derivados [Au(AH3)Cl] (1) y [Cu(AH3)2(H2O)2](NO3)2 (2) fueron sintetizados y caracterizados por técnicas espectroscopias como RMN 1H ,13C, UV-vis, infrarrojo y análisis elemental. Se investigaron las interacciones de estos compuestos sobre dos blancos moleculares el ADN y la TrxR. Los resultados encontrados sugirieren que estos complejos metal-azasterol interactúan con el ADN covalentemente. El complejo 1 también mostró tener la capacidad de inhibir fuertemente la TrxR. Además, fueron evaluadas sus actividades contra Sporothrix spp., encontrando que complejo 1 fue el más activo, incluso mejor que el itraconazol.

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 electron-density 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.