Rhododendron ferrugineum L. (Ericaceae), an evergreen shrub
that grows on acid soil just above the tree line in the Pyrenees
and the Alps, is one of the few rhododendron species occurring in
Europe.1 An aqueous decoction of the leaves has been used in
traditional medicine against ailments such as rheumatism, hypertension,
neuralgia, and myalgia.1,2 Previous phytochemical
research led to the isolation of phloracetophenones,3 phloracetophenone
glucosides,3 dihydroflavonol glycosides,4 and flavonoid
glycosides5 from the flowers and the leaves of this species.
Rhododendron species are known as toxic plants, causing intoxications
in animals and poisoning in humans by contaminating
honey. The latter is characterized by gastrointestinal tract symptoms,
hypotension, and bradycardia and is attributed to the
grayanotoxin polyhydroxylated diterpenes.6 Although the toxicity
of R. ferrugineum in animals has been reported, there are no data
regarding its effects in humans. Recently, Louis and co-workers
have shown that an aqueous extract of R. ferrugineum exerts no
negative influence on cell activity.5 However, a toxic effect of this
species is feasible, at least in part due to the possible presence of
grayanotoxins.On the basis of the toxicity of Rhododendron species,
R. ferrugineum indicates a potential source of cytotoxic compounds.
Hence, the present work is aimed at investigating the cytotoxicity of
the nonpolar extract of R. ferrugineum and its components.
The cytotoxicity of the chloroform-soluble fraction of R. ferrugineum
was demonstrated, and the bioassay-guided isolation and
characterization of compounds responsible for the cytotoxicity of
the plant conducted.We report herein the purification and structure
elucidation of the newcompounds 13, aswell as the isolationof 12
known compounds. Compounds 13 were evaluated for