Potencial antifúngico e modulador de nerolidol e alfa- bisabolol sobre a sensibilidade de trichophyton spp. a griseofulvina.

Abstract

Dermatophytes is a name given to a group of fungi specialized in invading and colonizing keratinized tissues such as skin, hair and nails of humans and animals, causing the dermatophytosis or tinea. Dermatophytosis has a global distribution and is considered a public health problem. Among the dermatophytes Trichophyton rubrum is responsible for the highest incidence in the cases of tinea pedis, tinea capitis and tinea unguium. With the reduced number of classes of antifungal drugs (azole, allylamine, griseofulvin) available in the market and the growing phenomena of fungal resistance, new ways of implementing antifungal therapy have been sought. Thus, natural products such as terpenes appear as a valid alternative, in view of their antimicrobial characteristics. Sesquiterpenes are natural products found in essential oils which represent an alternative to mechanisms of fungal resistance such as the expression of efflux pumps, and the undesirable effects of conventional drug therapy

such as griseofulvin. Therefore, the antifungal and modulatory activity of the sensitivity of α- bisabolol and nerolidol in T. rubrum, T. interdigitale H6 and T. interdigitale Δmdr2 to

griseofulvin were investigated. The minimum inhibitory concentration (MIC) of test drugs was determined by microdilution. Subsequently, the effect of drug-testing on plasma membrane functionality (K +

release) was analyzed. The MIC of griseofulvin was determined at subinibtial concentrations of sesquisterpenes or chlorpromazine (modulation assay). Finally, an association study was performed with griseofulvin and sesquisterpenos (checkerboard). α-bisabolol was more potent than nerolidol because it presented 32-fold lower MIC values. All fungi susceptible to griseofulvin from 8 μg / mL. With the exception of griseofulvin, all drug-tests increased the release of K +

(p <0.05), affecting the functionality of the plasma membrane. Nerolidol modulated the susceptibility to griseofulvin of all strains and α-bisabolol modulated the sensitivity only of T. interdigitale H6 and T. interdigitale Δmdr2. In this study, we observed that chlorpromazine did not modulate the sensitivity of the fungus T. rubrum LM 4 to griseofulvin and may be due to non-expression of ABC transporter proteins, since clopromazine is a recognized blocker of efflux pumps. Thus, it is suggestive that the modulation possibly does not involve interference in the activity of ABC transporters encoded by the mdr2 gene. Nerolidol α-bisabolol presented synergism and additivity, respectively, in association with griseofulvin. Finally, the results of our study suggest the potential use of α-bisabolol and nerolidol compounds as antifungal agents and modulators of the sensitivity of Trichophyton spp to griseofulvin. This information may be useful for research aimed at clinical applications of α-bisaolol and nerolidol in the treatment of dermatophytosis, especially in T. rubrum infections. However, further studies are needed for the development of formulations and applications of such compounds in antifungal therapy.