α-Bisabolol from Chamomile – A specific ergosterol biosynthesis inhibitor?
Summary
There is a strong need for new antifungal agents with a different mode of action
due to the therapeutic limitations of existing drugs and the development of
fungal resistances ([NIAID, The second NIAID workshop in medical mycology:
molecular and immunologic approaches to the diagnosis and treatment of systemic
mycoses, http://www.niaid.nih.gov/dmid/meetings/mycology94/fungal.htm (2001)]).
Mammalians, plants and fungi produce at least different cell wall sterols from
common precursors. No antifungal drug is known that specifically prevents the
formation of the fungal ergosterol, without affecting sterol biosynthesis at
early, common stages (DiDomenico, B., Novel antifungal drugs, Curr Opin
Microbiol 1999;2:509–15; Walsh TJ, Viviani MA, Arathoon E, Chiou C, Ghannoum M,
Groll AH, et al., New target and delivery systems for antifungal therapy, Med
Mycol 2000;38(Suppl. I):335–47). To find new inhibitors that may inhibit
ergosterol biosynthesis, a query of a database on antimicrobials (Pauli, A.,
AmicBase 2005. Weinheim, New York: Wiley, 2005a; Pauli, A., Anticandidal low
molecular compounds from higher plants with special reference to compounds from
essential oils. Med Res Rev doi:10.1002/med.20050; 2005b) was performed with
substructures of intermediates of ergosterol biosynthesis. As a result a series
of Candida albicans-inhibiting compounds were identified that all possess the
side chain of zymosterol as a substructure; their anticandidal activity was
found to be increased with increase of their molecular volume. The entire
structure of the Chamomile constituent α-bisabolol is found as a substructure in
similar form within zymosterol. It was therefore concluded that compounds of
this type interfere with ergosterol biosynthesis at the level of zymosterol and
prevent the formation of fecosterol from zymosterol, which is the first fungi
specific step in ergosterol biosynthesis. Due to the low toxicity of α-bisabolol
(Schilcher H, Wirkungsweise und Anwendungsformen der Kamillenblüten, BMV
Berliner Medizinische Verlagsanstalt GmbH, Berlin; 2004) the compound comes into
question as a therapeutic agent and may serve as a lead compound in the
development of new antifungal drugs.
note: a-Bisabolol 天然紅沒藥醇