Validação, atividade antifúngica e avaliação sinérgica de nitroestirenos in vitro

Abstract

Nitro compounds have been used in therapy from the 40s, when they were widely synthesized and tested against various diseases as well as the discovery of their cytotoxic effects. Thus different groups, derivatives and analogs which could prove safer and more effective were studied. Some studies have shown that nitrostyrenes, like the nitrofenileteno possess diverse biological activities such as antifungal, antibacterial, anti-inflammatory, antinoceptive, etc. Additonally, there is currently a growing interest in new antifungal agents. Among the fungi of the genus Aspergillus is the most common Aspergillus fumigatus which is transmitted through the air causing aspergillosis. Dermatophytes are clinically relevant and cause various skin diseases, Trichophyton mentagrophytes being quite prevalent. The objective of this study was to validate the chemical structure of synthesized nitrostyrenes and evaluate its antifungal activity in two species of fungi, including a filamentous dermatophytes and opportunistic as well as evaluation of the synergistic effects among nitrostyrenes and amphotericin B (AB). The results confirm the infrared spectral and nuclear magnetic resonance of 1H nitrostyrenes analogues as correspond with the proposed structure. Test microdilution demonstrated in vitro antifungal activity of nitrostyrenes with MIC values for 4'-methyl-1-nitro-2- phenylethene (7B) of 0,05 mg/ml against A. fumigatus. For T. mentagrophytes the most active compound was 4'-methoxy-1-nitro-2-phenylethene (7C) with MIC of 0,22 mg/mL. Regarding the analysis of the combination of AB and nitrostyrenes in vitro by the checkerboard test showed antagonist compound 7A and 7C. The 7B compound was indifferent against the standard strain of A. Fumigatus.