SILVA, E. P.; http://lattes.cnpq.br/0601853644678240; SILVA, Emanuel Pereira.
Résumé:
Dermatophytoses are fungal infections involving the invasion and propagation of
dermatophytes in keratinized structures. Despite the numerous medications available
in the market for treating these conditions, resistance to conventional antifungals has
been on the rise, leading to therapeutic failures. Currently, the ability of dermatophytes
to produce biofilms is considered one of the most important factors involved in
treatment failures, as these biofilms hinder the penetration of drugs into infected
tissues. Therefore, research aimed at finding new antifungal agents with potential anti-
biofilm properties is crucial. In this regard, riparins, a class of alkaloids containing an
amide group, isolated from the green fruits of Aniba riparia, are promising
phytochemicals. In this study, we assessed the antifungal and anti-biofilm activity of
riparin 3 (RIP3) and its synthetic counterpart Nor-(NOR3) against clinically relevant
dermatophytes Trichophyton rubrum, Microsporum canis, and Nannizzia gypsea.
Cyclopirox (CPX) was used as the positive control. The effects of RIP3 and NOR3 on
fungal growth were evaluated using the microdilution technique. The quantification of
in vitro biofilm biomass was carried out using 0.5% crystal violet, and biofilm viability
was assessed by quantifying the number of colony-forming units (CFUs). The ex vivo
model was performed on human nail fragments, which were evaluated through light
microscopy and quantification of CFUs (viability). Finally, it was determined whether
the test drugs inhibited the sulfite secretion by strains grown in M9 medium with L-
cysteine, based on sulfite oxidation to sulfate and measurement of stable signal at 570
nm. The results showed that RIP3 is a fungicide, inhibiting the growth of T. rubrum and
M. canis from 128 mg/L and N. gypsea from 256 mg/L onwards. Conversely, NOR3
showed no antifungal activity against the tested dermatophytes (MIC > 1024 mg/L).
Regarding anti-biofilm activity, RIP3 inhibited the in vitro and ex vivo biofilm formation
and viability compared to the control (p <0.05). Furthermore, RIP3 significantly
inhibited sulfite secretion and was more potent than CPX. In conclusion, the results
indicate that RIP3 is a promising antifungal agent against dermatophyte biofilms, and
this action appears to involve the inhibition of sulfite secretion.
