Anti-dermatophyte activity of Leguminosae plants from Southern Brazil with emphasis on Mimosa pigra (Leguminosae).

BACKGROUND: Intensive prophylactic use of antifungals leads to the increase of drug resistance and the need for new and more effective treatments are real. Plants from Leguminosae family are rich in flavonoids, for which numerous biological activities have been described, including antifungal effects. PURPOSE: To screen methanolic extracts from Leguminosae species looking for alternative sources for antifungal agents (anti-dermatophyte and anti-Candida) and their innocuity. METHODS: Antifungal activity was evaluated using the strains Candida albicans, C. krusei, C. glabrata, C. tropicalis, C. parapsilosis, Epidermophyton floccosum, Trichophyton mentagrophytes, T. rubrum and, Microsporum gypseum in the broth microdilution method. Later, the minimum inhibitory concentration (MIC) for Mimosa pigra, Eriosema heterophyllum, and Chamaecrista nictitans was determined. The most promising extract was fractionated and cytotoxicity and genotoxicity of the most active fraction were also assayed. RESULTS: Fungicide and/or fungistatic activity against dermatophyte strains were presented by 60% of the methanolic extracts assayed. M. pigra, E. heterophyllum, and C. nictitans methanolic extracts could inhibit dermatophyte strains at concentrations ranging from 1.9 to 1000µg/mL. M. pigra showed the lowest MIC values for a dichloromethane fraction (1.9µg/mL) without DNA damage at 10 and 50µg/mL and 100% of cell viability of human leukocytes. CONCLUSION: Our results indicate that methanolic extracts from Leguminosae plants are potential sources of antifungal compounds, mainly the extract and fractions from M. pigra. The dichloromethane fraction from M. pigra did not showed in vitro toxicity according to the applied assays.

[Resistance to azolic compounds in clinical Trichophyton spp. strains]. / Resistencia a compuestos azólicos de aislamientos clínicos de Trichophyton spp.

The increase of dermathophytosis in patients with poor therapeutic response leads us to study the antifungal susceptibility of 36 clinical isolates to itraconazole, ketoconazole and fluconazole by the E-test method. According to established parameters by the Clinical Laboratory Standards Institute, the resistance to one or more antifungal drugs was demonstrated in seven isolates (19.4%) as follows: three Trichophyton rubrum, three T. mentagrophytes and one T. tonsurans. A T. rubrum isolate was resistant to the three azolic drugs; the other six only to fluconazole. It is important to establish the antifungal susceptibility as part of the study procedures in patients with dermatophytosis and a poor antifungal response.

Dermatophytes growth curve and in vitro susceptibility test: a broth micro-titration method.

The introduction of systemic antifungal drugs which act upon different targets is the main issue of the in vivo antifungal resistance control. Different factors, such as growth curve phase, quality of the specimen, quantity of the inoculum, temperature, pH, culture medium composition, incubation duration and solvent, are believed important factors affecting minimum inhibitory concentration (MIC) value to most of the antifungal agents. We assayed an in vitro susceptibility test with 40 isolates of dermatophytes: Microsporum canis, Trichophyton rubrum, Trichophyton mentagrophytes and Epidermophyton floccosum against griseofulvin, fluconazole, itraconazole and terbinafine, using the guidelines of the M38-P document approved by the NCCLS. We determined the growth curves, to estimate the specific growth rate (mu max) and the generation time (G) of each dermatophyte, using dry weight and spectrophotometry methods. We demonstrate that, at 192 h, all fungi tested had a constant growth curve and we considered this as the optimal time for MIC determination. Terbinafine, griseofulvin and itraconazole possessed the highest antifungal activity against the four groups of dermatophytes studied. Fluconazole demonstrated no efficacy. Our MIC results differ from other authors and this difference is due to the timing of the MIC determination based on the growth curve of each fungi tested.

Chemical analysis and antifungal activity of the essential oil of Calea clematidea.

The chemical composition of the essential oils of Calea clematidea Baker obtained by hydrodistillation of the leaves and flowers was analysed by GC and GC/MS and the oils were assayed for their antifungal activities. The essential oil of the leaves showed a high content of a new natural epoxy terpenoid, named clemateol (ca. 70 %), with minor amounts of o-vanillin (6.5 %), spathulenol (4.2 %), alpha-terpinene (4.0 %), germacrene B (2.9 %), yomogi alcohol (1.8 %), ( E)-caryophylene (1.7 %), m-cymenene (1.6 %), and alpha-gurjunene (1.5 %), while the essential oil of the flowers was characterized by a higher content of thymol methyl ether (ca. 80 %), with minor amounts of clemateol (4.8 %) and o-cymene (4.7 %). The antimicrobial activity of the oils was also evaluated against dermatophytes for their possible use in pharmaceutical preparations for topical applications. The oil of the leaves (MIC > 3.57 mg/ml), clemateol (MIC > 1.52 mg/ml), and the alcohol 2 (MIC > 2.82 mg/ml) showed a moderate antifungal activity against Trichophyton tonsurans, Trichophyton rubrum, Trichophyton menthagrophytes var. i nterdigitale, Epidermophyton floccosum, Microsporum gypseum, Microsporum canis and Microsporum nanum.

Efficacy of ozonized sunflower oil in the treatment of tinea pedis.

Ozonized sunflower oil, Oleozon, has a remarkable gerrmicidal action. In the present study, the efficacy of Oleozon in the treatment of tinea pedis was demonstrated in a controlled randomized phase III assay, comparing topical Oleozon with ketoconazole cream 2% (Nizoral) in 200 patients (100 in each group). The treatment administered was twice per day for a period of 6 weeks. The efficacy was evaluated clinically (disappearance of all lesions, with or without negative mycological results) and mycologically (negative culture results). A complete clinical and mycological cure was obtained in 75 and 81% for Oleozon and ketoconazole, respectively, with no significant differences between both groups. No side-effects or bacterial super-infections were observed. Patients were evaluated 6 months after the end of the treatment and no recurrence was observed in the Oleozon group. Oleozon can be an effective alternative low-cost antimycotic drug.

Inhibitors of the fungal cell wall. Synthesis of 4-aryl-4-N-arylamine-1-butenes and related compounds with inhibitory activities on beta(1-3) glucan and chitin synthases.

As part of our project devoted to the search for antifungal agents, which act via a selective mode of action, we synthesized a series of new 4-aryl- or 4-alkyl-N-arylamine-1-butenes and transformed some of them into 2-substituted 4-methyl-tetrahydroquinolines and quinolines by using a novel three-step synthesis. Results obtained in agar dilution assays have shown that 4-aryl homoallylamines not possessing halogen in their structures, tetrahydroquinolines and quinolines, display a range of antifungal properties in particular against Epidermophyton floccosum and Microsporum canis. Regarding the mode of action, all active compounds showed in vitro inhibitory activities against beta(1-3) glucan-synthase and mainly against chitin-synthase. These enzymes catalyze the synthesis of beta(1-3) glucan and chitin, respectively, major polymers of the fungal cell wall. Since fungal but not mammalian cells are encased in a cell wall, its inhibition may represent a useful mode of action for these antifungal compounds.

In vitro evaluation of antifungal properties of 8.O.4'-neolignans.

Eighteen racemic 8.O.4'-neolignans with six different substitution patterns in rings A and B, in their ketone and in their erythro and threo alcoholic forms, were evaluated for antifungal activity by the agar dilution method. Only the alcohols exhibited a broad spectrum of activities against Microsporum canis, Microsporum gypseum, Tricophyton mentagrophytes, Tricophyton rubrum, and Epidermophyton floccosum. (+/-)-erythro-3,4-(methylenedioxy) -7-hydroxy-1'-allyl-3',5'-dimethoxy-8.O.4'-neolignan (11) was the most active compound in the series, and E. floccosum was the most susceptible species.

Plants used in Guatemala for the treatment of dermatophytic infections. 2. Evaluation of antifungal activity of seven American plants.

From 52 plants screened for antifungal activity, 26 (50%) were active against dermatophytes. This paper reports further evaluation of seven American plants against four pathogenic fungi (Aspergillus flavus, Epidermophyton floccosum, Microsporum gypseum and Trichophyton rubrum), the part showing most activity, the best solvent and, in three cases, the minimal inhibitory concentration (MIC) against the fungus in pure culture. Antifungal activity was confirmed in all of the plants, but not all parts; the most active parts were the bark and leaves. The most active species were Byrsonima crassifolia, Cassia grandis, Gliricidia sepium and Malpighia glabra. Diphysa robinioides, Rhizophora mangle and Cassia occidentalis were less active. The most susceptible fungi were E. floccosum and T. rubrum; A. flavus was not susceptible. Ethanol was usually the best solvent and the MIC of C. grandis, C. occidentalis and D. robinioides was 50 micrograms/ml.

Atividade antifungica in vitro de óleos essenciais frente a isolados clínicos de dermatófitos / In vitro antifungal activity of essential oils against clinical isolates of dermatophytes

Resumo:Oleos essenciais de Annona crassiflora (araticum) Cymbopogon citratus (capim santo), Cinnamomum zeylanicum (canela), Ocimum gratissimum (alfavaca), Protium heptaphyllum (almiscar), Xylopia frutescens (embiriba vermelha) foram ensaiados contra várias cepas e Microsporum canis, Trichophyton rubrum, trchophyton mentagrophytes e Epidermophyton floccosum isolados de pacientes com dermatofitoses. Essas plantas säo popularmente utilizadas no nordeste brasileiro para tratamento de infecçöes da pele e seus anexos, causadas por bactérias, vírus e fungos. Cinco dos óleos essenciais ensaiados mostraram excelente atividade antifúngica inibindo fortemente o crescimento e 81 (por cento) das cepas estudadas. O óleo de P. heptaphyllum foi completamente inativo (au)