RESUMEN

Thirty-four arylpropanoids and related compounds were evaluated in vitro for antifungal properties. Among them, 22 phenyl-, 4 naphthyl-, and 4 phenanthrylpropanoids; naphthalene; phenanthrene; and 2-chloro-1-hexyl-1-propanone were tested against dermatophytes by the agar dilution method. alpha-Halopropiophenones exhibited a broad spectrum of activities against Microsporum canis, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum, and Epidermophyton floccosum, with MIC values between 0.5 and >50 microg/mL. Keto, alcohol, and alpha-haloketo propyl derivatives of naphthalene and phenanthrene also showed very good activity against all dermatophytes tested, clearly showing that in these series, a halogen atom is not necessary for activity. Phenanthryl derivatives were more active (MICs, 3-20 microg/mL) than naphthyl ones (MICs, 3-50 microg/mL). A structure-activity relationship study was carried out and aided in establishing the structural requirements of arylpropanoids for antifungal activities. Because dermatophytes are a group of fungi that characteristically infect the keratinized areas of the body, these new series of antifungal compounds open the possibility of discovering new topical antifungal drugs for the treatment of dermatomycoses, which are frequently very difficult to eradicate.

Asunto(s)

RESUMEN

This study describes the fungistatic effect of xanthoxyline (CAS 90-24-4) and its derivatives against a panel of yeasts, filamentous fungi and dermatophytes, by using the agar dilution method. Results indicated that simple structural modifications led to more potent derivatives, especially in relation with dermatophytes. The most active compound tested (10), which is a benzenesulphonyl derivative, was 12-fold more potent than xanthoxyline itself against Trichophyton rubrum. The evaluation of the mode of action with the whole cell Neurospora crassa assay, suggested that some selected compounds may be acting by the inhibition of fungal cell-wall polymers synthesis or assembly.

Asunto(s)

RESUMEN

Neutral racemic antifungal alcohols of 8.O.4'-neolignan type, were evaluated for inhibitory activity towards the fungal cell wall, using the whole cell Neurospora crassa hyphal growth inhibition assay. Results strongly suggested that these compounds could act by inhibiting cell wall polymer synthesis or assembly. Active compounds were tested for their inhibitory activities against (1,3)-beta-glucan synthase, an enzyme that catalyzes the synthesis of the major wall polymer (1,3)-beta-glucan. Although these compounds were found to be inhibitors of the enzyme (inhibition ranging between 2 and 72% at 250 micro/ml), comparison of these results with those from agar dilution assays, allow us to infer that these compounds do not act via the inhibition of glucan synthase. In addition, ketones with same pattern of substitution as alcohols, which have no antifungal properties in agar dilution assays, still displayed similar glucan synthase inhibition.

Asunto(s)

RESUMEN

Twenty nine extracts belonging to eight species of the Argentine flora reported as antifungal in folk medicine, were assayed for antifungal properties by using the agar dilution method, against a panel of yeasts, filamentous fungi as well as dermatophytes. Nine extracts belonging to six species, exhibited a broad spectrum of activity against Microsporum cants, Microsporum gypseum, Trichophyton mentagrophytes, Trichophyton rubrum and Epidermophyton floccosum, with MICs ranging from 25 to 900 µg/ml. A dichloromethanis extract of Polygonum ferrugineum was the most active extract with MICs from 25-50 µg/ml. To gain an insight into the mode of action of the active extracts they were evaluated for their inhibitory activities toward the fungal cell wall, using the whole cell Neurospora crassa hyphal growth inhibition agar diffusion assay. A hazy zone around the paper disk strongly suggested that the dichloromethane extracts from aerial parts of Polygonum punctatum, Polygonum ferrugineum and the bark of Luehea divaricata acted by inhibiting polymer synthesis or assembly of the cell wall. The clear zone of inhibition produced by the dichloromethane and methanol antifungal extracts of Xanthium spinosum could be ascribed to the fact that these extracts have another effect on fungal cells in addition to inhibition of cell walls.