Avaliação in vitro e in vivo da atividade antifúngica de aliliminas

Abstract

Cryptococcosis is an invasive mycosis of worldwide occurrence, mainly caused by Cryptococcus neoformans and Cryptococcus gattii and affects patients both immunocompromised as immunocompetent. Its treatment may be complicated by the toxicity of the drugs used and the emergence of resistant strains. The discovery of new antifungals that solve this situation is crucial for effective treatment of fungal infections. The allylimines have similar structures to the group of allylamines, containing a double bond next to the nitrogen atom in the molecule. A screening test was performed with 22 allylimines against C. neoformans and C. gattii; six compounds were selected to investigate their antimicrobial activity and toxicity. These substances showed greater activity against Cryptococcus spp. and Fonsecaea pedrosoi and unsatisfactory results against Candida spp., Aspergillus spp. and some bacteria. From the toxicity tests the allylimine 3H2 was selected for further anticryptococcal activity studies. It showed fungistatic activity against C. gattii samples and fungicidal against C. neoformans. The allylimine 3H2 shown to be indifferent in combination with fluconazole, however showed synergism when combined with amphotericin B. The allylimine tested was able to slow the melanin synthesis, reduce laccase activity and decrease the capsule production in a C. gattii strain. In vivo the compound tested individually was not effective in the treatment of mice infected with C. gattii but showed synergism with amphotericin B, prolonging the survival of animals and reducing the fungal load in the groups treated with this association. Thus, this compound proves to be a promising antifungal agent that it could be used as alternatives in the treatment and control of serious fungal infections such as cryptococcosis.