Atividade antifúngica da riparina e seus derivados: efeito sobre o crescimento e o biofilme dos dermatófitos.

Abstract

Dermatophytosis, one of the most common superficial mycoses in the world, is mainly associated with infections by the dermatophytes Trichophyton rubrum and Microsporum canis. Biofilm production is an essential factor in the pathogenesis of dermatophytes, as it confers resistance and recalcitrance to the drug, which significantly impairs the effectiveness of antifungal agents. Systemic therapeutic alternatives are used as treatment, such as pills and local creams and ointments, such as Fluconazole and Griseofulvin. Therefore, we evaluated the antibiofilm effect of riparin 1 (RIP1), an alkaloid-like alkaloid, against clinically relevant dermatophytes. We have also produced synthetic homologues of nor (NOR1) and dinor (DINOR1) for pharmacological evaluation, with a yield of 61-70%. We used in vitro (96-well polystyrene plates) and ex vivo (hair fragments) models to verify the effects of these compounds on biofilm formation and viability. RIP1 and NOR1 showed antifungal activity against T. rubrum and M. canis strains, but DINOR1 did not show significant antifungal activity against dermatophytes. Furthermore, RIP1 and NOR1 significantly reduced the viability of biofilms in vitro and ex vivo (p < 0.05). However, RIP1 was more potent than NOR1, possibly due to the distance between p-methoxyphenyl and phenylamide structures. In conclusion, RIP1 and NOR1 have significant antifungal and antibiofilm activities, demonstrating potential to be used in the development of drugs aimed at the treatment of dermatophytosis.