Adamantylidene-substituted alkylphosphocholine TCAN26 is more active against Sporothrix schenckii than miltefosine

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 ag...

Full description

Saved in:
Bibliographic Details
Published in:Memórias do Instituto Oswaldo Cruz 2016-08, Vol.111 (8), p.523-527
Main Authors: Borba-Santos, Luana Pereira, Ishida, Kelly, Calogeropoulou, Theodora, Souza, Wanderley de, Rozental, Sonia
Format: Article
Language:English
Subjects:
Adamantane - chemistry
Adamantane - pharmacokinetics
antifungal
Antifungal Agents - chemistry
Antifungal Agents - pharmacology
Cell Membrane - drug effects
Drug Substitution
Humans
Microbial Sensitivity Tests
Microscopy, Electron, Scanning
Microscopy, Electron, Transmission
miltefosine analogue
PARASITOLOGY
Phosphorylcholine - analogs & derivatives
Phosphorylcholine - chemistry
Phosphorylcholine - pharmacology
Short Communication
Sporothrix - classification
Sporothrix - drug effects
Sporothrix - ultrastructure
Sporothrix schenckii
TROPICAL MEDICINE
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:0074-0276
1678-8060
1678-8060
DOI:10.1590/0074-02760160088