Anti-dermatophyte constituents of the essential oil from the root of Ferula hermonis
In a previous work, the essential oil from the dried root of Ferula hermonis Boiss. (Umbelliferae), whose major constituents were alpha-pinene (43.3%), alpha-bisabolol (11.1%) and the unusual acetylene 3,5-nonadiyne (4.4%), showed moderate antifungal activity against Trichophyton mentagrophytes . With the aim of characterizing the active constituents, a bioguided fractionation of the essential oil was performed. Twenty seven fractions were obtained and submitted to GC-FID, GC-MS and 13C-NMR analyses, as well as to an agar overlay bioautographic assay for the detection of the activity against T. mentagrophytes and Microsporum gypseum. Growth inhibition zones of different magnitudes were observed in the case of fraction 2, fraction 10 and from fraction 17 to 27. In fraction 2 the activity was directly related to alpha-pinene, whereas in fraction 10 the major constituent was 3,5-nonadiyne. Successive fractionation of the essential oil allowed the isolation of the main constituents of the active fractions 17 to 27: alpha-bisabolol, alpha-bisabolol oxide B, trans-verbenol, jaeschkeanadiol angelate, and two purified fractions, one of them with 73% of jaeschkenadiol benzoate and the other with 50% of spathulenol. Activity against both dermatophytes was evaluated from the MIC and MFC values, which ranged from 0.25 to 128µg/ml. The most potent activity was demonstrated by the fraction with 73% jaeschkeanadiol benzoate against T. mentagrophytes, with the same MIC and MFC values of 0.25µg/ml, equivalent to that one of ketoconazole (0.25µg/ml) and superior to amphotericin B (0.5µg/ml) and nystatin (2µg/ml). Both dermatophytes were highly sensitive to the unusual compound 3,5-nonadiyne whose MIC and MFC's for T. mentagrophytes were 8µg/ml, whereas in the case of M. gypseum MFC value was about two-fold the MIC value (8 and 16µg/ml, respectively).
Acknowledgements: AA Bdwan, JPM (Naor, Jordan) and TS El-Thaher, ARAGEN Biotechnology (Naor, Jordan) for providing plant material.
References: 1. Al-Ja'fari AH et al. (2008) 7th Joint Meeting of AFERP, ASP, GA, PSE & SIF, Athens, Greece.