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. Apr-Jun 2018;49(2):407-413.
doi: 10.1016/j.bjm.2017.06.009. Epub 2017 Oct 12.

A New Coumarin Derivative, 4-acetatecoumarin, With Antifungal Activity and Association Study Against Aspergillus Spp

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A New Coumarin Derivative, 4-acetatecoumarin, With Antifungal Activity and Association Study Against Aspergillus Spp

Felipe Q S Guerra et al. Braz J Microbiol. .
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Abstract

Fungal infections have become a concern for health professionals, and the emergence of resistant strains has been reported for all known classes of antifungal drugs. Among the fungi causing disease, we highlight those that belong to the genus Aspergillus. For these reasons, the search for new antifungals is important. This study examines the effects of a coumarin derivative, 4-acetatecoumarin (Cou-UMB16) both alone and together with antifungal drugs, and its mode of action against Aspergillus spp. Cou-UMB16 was tested to evaluate its effects on mycelia growth, and germination of Aspergillus spp. fungal conidia. We investigated its possible action on cell walls, on the cell membrane, and also the capacity of this coumarin derivative to enhance the activity of antifungal drugs. Our results suggest that Cou-UMB16 inhibits Aspergillus spp. virulence factors (mycelia growth and germination of conidia) and affects the structure of the fungal cell wall. When applying Cou-UMB16 in combination with azoles, both synergistic and additive effects were observed. This study concludes that Cou-UMB16 inhibits mycelial growth and spore germination, and that the activity is due to its action on the fungal cell wall, and that Cou-UMB16 could act as an antifungal modifier.

Keywords: A. flavus; A. fumigatus; Antifungal activity; Coumarin; Mode of action.

Figures

Fig. 1
Fig. 1
Chemical structure for 4-acetatecoumarin (Cou-UMB16).
Fig. 2
Fig. 2
Percentage of conidial germination of A. fumigatus (ATCC 46913), A, and A. flavus (ATCC 16013), B, in the absence (control) and presence of 4-acetatecoumarin (MIC: 16 μg/mL; 2 × MIC: 32 μg/mL) and amphotericin B (MIC: 2 μg/mL; 2 × MIC: 4 μg/mL). a: p < 0.05 compared to control. b: p < 0.05 compared to amphotericin B with respective concentration.
Fig. 3
Fig. 3
Percentage of dry mycelia weight produced by A. fumigatus (ATCC 46913), A, and A. flavus (ATCC 16013), B, in the absence (control) and presence of 4-acetatecoumarin (MIC: 16 μg/mL; 2 × MIC: 32 μg/mL) and amphotericin B (MIC: 2 μg/mL; 2 × MIC: 4 μg/mL). Control produced 100% of dry mycelia weight. a: p < 0.05 compared to control. b: p < 0.05 compared to amphotericin B with respective concentration.

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