ABSTRACT
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.
Subject(s)
Humans , Adamantane/pharmacokinetics , Antifungal Agents/pharmacology , Phosphorylcholine/analogs & derivatives , Sporothrix/drug effects , Adamantane/chemistry , Antifungal Agents/chemistry , Cell Membrane/drug effects , Drug Substitution , Microbial Sensitivity Tests , Microscopy, Electron, Scanning , Microscopy, Electron, Transmission , Phosphorylcholine/chemistry , Phosphorylcholine/pharmacology , Sporothrix/classification , Sporothrix/ultrastructureABSTRACT
Sporotrichosis is a rare profound mycosis exsisting in a sporadic state in Morocco. A calrification of this disease is proposed. A general review on sporotrichosis was performed using Medlines data base, the articles published during the last ten years were analyzed. We gave priority to works dealing particularly with the biological aspects of the mycosis. The particular biotope of the parasitic development and its mode of contamination explain its rarity in Morocco. According to the fungal way of penetration and the immune state of the host, 4 clinical forms were described: the lymphocutaneous, pure cuteneous, pulmonary and disseminated form. As the direct examination exceptionally visualizes the spors, culture on Sabouraud medium was performed to do a mycological diagnosis which approved the presence of fine and ramified myceliums. Treatment depends on the clinical forms: itraconazale in the cutaneous and osteo-articular sporotrichosis and the amphotaricin B in the pulmonary form