Avaliação da atividade antifúngica de carvacrol isolado e associado a anfotericina B frente a cepas de Aspergillus flavus isolado de material biológico

Abstract

Fungi comprise a group of pathogens that can cause serious health damage. Aspergillus flavus is among the main causes of serious comorbidities, among them, aspergillosis. Current afungal therapy has been increasingly inefficient, due to a series of issues related to adaptive mechanisms of the fungal cell itself or even due to toxicity associated with the high doses necessary for them to have the desired effect. In view of this, the search for new substances that may have antifungal effects through different mechanisms of action has been increasing. Natural products are a strong ally for these findings, since they are phytoconstituents of plant origin that have different biological activities. Among these, carvacrol stands out, a monoterpene found mainly in plants such as Origanum vulgare (oregano). Therefore, the objective of this work was to investigate the antifungal action of carvacrol and the licensed antifungals amphotericin B, fluconazole and voriconazole against clinical isolates of A. flavus. Assays to evaluate the biological activities were performed using the microdilution technique to determine the minimum inhibitory concentration (MIC), minimum fungicidal concentration (CFM), association studies and study of possible mechanisms of action. In the results of biological activity, it was observed that carvacrol at a concentration of 16 μg/ml inhibited the growth of most fungal strains, followed by amphotericin B, with MIC values of 32 μg/mL, fluconazole with 512 μg/mL and voriconazole with 1 μg/mL. As for the CFM assays, values of 32 μg/mL for carvacrol were observed, representing a fungicidal effect for the substance in question. Drug association assays are currently very well seen, because in addition to reducing the effective concentration of each substance, thus reducing the risk of toxicity, the use of more than one mechanism of action can be a very viable alternative in the fight against serious fungal pathologies. , thus, the association of carvacrol with amphotericin B represented ICIF values of 0.875, being considered an association of additivity. The proposed mechanism of action for carvacrol against A. flavus isolates was obtained from the sorbitol and ergosterol assays, where we can observe an action of the substance against the ergosterol of the fungal cell membrane, causing its imbalance and leading to cell death. fungal. Thus, carvacrol presents itself as a good candidate in the search for the development of new therapeutic alternatives that will meet the current needs in the face of the fungal pathologies in question.