Abstract
Background Dermatophytes belonging to theTrichophytongenus are important
human pathogens, but they have developed resistance to griseofulvin, the
most common antifungal drug used to treat dermatophytosis. Objective
This study was aimed to evaluate the antidermatophytic activity of
synthetic peptides, as well as mechanisms of action and synergistic
effect with griseofulvin. Methods Scanning electron microscopy (SEM),
atomic force microscopy (AFM) and fluorescence microscopy (FM) were
employed to understand the activity and the mechanism of action of
peptides. Results Here we report that synthetic peptides at 50 mu g/mL,
a concentration 20-fold lower than griseofulvin, reduced the
microconidia viability ofT. mentagrophytesandT. rubrumby 100%, whereas
griseofulvin decreased their viability by only 50% and 0%,
respectively. The action mechanism of peptides involved cell wall
damage, membrane pore formation and loss of cytoplasmic content.
Peptides also induced overproduction of reactive oxygen species (ROS)
and enhanced the activity of griseofulvin 10-fold against both fungi,
suggesting synergistic effects, and eliminated the toxicity of this drug
to human erythrocytes. Docking analysis revealed ionic and hydrophobic
interactions between peptides and griseofulvin, which may explain the
decline of griseofulvin toxicity when mixed with peptides. Conclusion
Therefore, our results strongly suggest six peptides with high potential
to be employed alone as new drugs or as adjuvants to enhance the
activity and decrease the toxicity of griseofulvin.
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