Therapeutic switching: from antidermatophytic essential oils to new leishmanicidal products.
This study examined whether the antidermatophytic activity of essential oils (EOs) can be used as an indicator for the discovery of active natural products against Leishmania amazonensis. The aerial parts of seven plants were hydrodistilled. Using broth microdilution techniques, the obtained EOs were tested against three strains of dermatophytes (Trichophyton mentagrophytes, Microsporum gypseum and Microsporum canis). To compare the EOs antifungal and antiparasitic effects, the EOs activities against axenic amastigotes of L. amazonensis were concurrently evaluated. For the most promising EOs, their antileishmanial activities against parasites infecting peritoneal macrophages of BALB/c mice were measured. The most interesting antifungal candidates were the EOs from Cymbopogon citratus, Otacanthus azureus and Protium heptaphyllum, whereas O. azureus, Piper hispidum and P. heptaphyllum EOs exhibited the lowest 50% inhibitory concentration (IC50) values against axenic amastigotes, thus revealing a certain correspondence between both activities. The P. hispidum EO was identified as the most promising product in the results from the infected macrophages model (IC50: 4.7 µg/mL, safety index: 8). The most abundant compounds found in this EO were sesquiterpenes, notably curzerene and furanodiene. Eventually, the evaluation of the antidermatophytic activity of EOs appears to be an efficient method for identifying new potential drugs for the treatment of L. amazonensis.
Centre National de la Recherche Scientifique, Institut Pasteur de la Guyane, Cayenne, French Guiana.
Emeline
E
Houël
Faculté des Sciences Pharmaceutiques, Université de Toulouse III-Paul Sabatier, Toulouse, France.
German
G
Gonzalez
École Nationale Supérieure de Chimie, Montpellier, France.
Jean-Marie
JM
Bessière
Centre National de la Recherche Scientifique-Guyane, Cayenne, French Guiana.
Guillaume
G
Odonne
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Véronique
V
Eparvier
Faculté des Sciences Pharmaceutiques, Université de Toulouse III-Paul Sabatier, Toulouse, France.
Eric
E
Deharo
Institut de Chimie des Substances Naturelles, Centre National de la Recherche Scientifique, Gif-sur-Yvette, France.
Didier
D
Stien
D000818:Animals; D000935:Antifungal Agents / Q000494:pharmacology*; D000981:Antiprotozoal Agents / Q000494:pharmacology*; D061245:Axenic Culture; D029403:Burseraceae / Q000378:metabolism; D031743:Cymbopogon / Q000378:metabolism; D057915:Drug Substitution; D005663:Furans / Q000008:administration & dosage; D008401:Gas Chromatography-Mass Spectrometry; D006574:Heterocyclic Compounds, 2-Ring / Q000008:administration & dosage; D020128:Inhibitory Concentration 50; D007891:Leishmania / Q000187:drug effects*; D017737:Macrophages, Peritoneal / Q000187:drug effects / Q000469:parasitology; D008807:Mice, Inbred BALB C; D008826:Microbial Sensitivity Tests; D008864:Microsporum / Q000187:drug effects; D009822:Oils, Volatile / Q000494:pharmacology*; D031701:Piper / Q000378:metabolism; D010943:Plantago / Q000378:metabolism; D012717:Sesquiterpenes / Q000008:administration & dosage; D014249:Trichophyton / Q000187:drug effects
D000935:Antifungal Agents; D000981:Antiprotozoal Agents; D005663:Furans; D006574:Heterocyclic Compounds, 2-Ring; D009822:Oils, Volatile; D012717:Sesquiterpenes; C442489:furanodiene