Synthesis, structure-activity relationships (SAR) and in silico studies of coumarin derivatives with antifungal activity.

The increased incidence of opportunistic fungal infections, associated with greater resistance to the antifungal drugs currently in use has highlighted the need for new solutions. In this study twenty four coumarin derivatives were screened in vitro for antifungal activity against strains of Aspergillus. Some of the compounds exhibited significant antifungal activity with MICs values ranging between 16 and 32 µg/mL. The structure-activity relationships (SAR) study demonstrated that O-substitutions are essential for antifungal activity. It also showed that the presence of a short aliphatic chain and/or electron withdrawing groups (NO(2) and/or acetate) favor activity. These findings were confirmed using density functional theory (DFT), when calculating the LUMO density. In Principal Component Analysis (PCA), two significant principal components (PCs) explained more than 60% of the total variance. The best Partial Least Squares Regression (PLS) model showed an r2 of 0.86 and q2(cv) of 0.64 corroborating the SAR observations as well as demonstrating a greater probe N1 interaction for active compounds. Descriptors generated by TIP correlogram demonstrated the importance of the molecular shape for antifungal activity.

A new coumarin derivative, 4-acetatecoumarin, with antifungal activity and association study against Aspergillus spp.

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.

Morphological alterations and time-kill studies of the essential oil from the leaves of Coriandrum sativum L. on Candida albicans / Alteraciones morfológicas y estudios de letalidad del aceite esencial de las hojas de Coriandrum sativum L. en Candida albicans

The objective of this study was to evaluate the morphological alterations and time-kill of the essential oil of the leaves of C. sativum L. on strains of C. albicans. The essential oil was submitted to gas chromatography-mass spectrometry analysis. The predominant component identified was linalool (39.78 percent). Minimal inhibitory concentration and minimal fungicidal concentration of the essential oil were respectively 512 and 1024 ug.mL-1 for 90 percent of the strains tested. In the time-kill curves, the essential oil showed a concentration-dependent fungicidal effect. In the micromorphology assay it caused a significant reduction in pseudohyphae, an important pathogenic factor of C. albicans.

El objetivo de este estudio fue evaluar las alteraciones morfológicas y de letalidad del aceite esencial de las hojas de C. sativum L. en cepas de C. albicans. El aceite esencial se presentó a gas análisis de espectrometría de cromatografía-masa. El componente predominante identificado fue linalol (39,78 por ciento). Concentración inhibitoria mínima y concentración mínima fungicida del aceite esencial fueron, respectivamente, 512 y 1.024 ìg.mL-1 para 90 por ciento de las cepas probadas. En las curvas el tiempo-matar, el aceite esencial mostró un efecto fungicida dependiente de la concentración. En el ensayo de micromorfología causó una reducción significativa en pseudohifas, un importante factor patógeno de C. albicans.