TOXIC INHIBITION OF SMOOTH-MUSCLE CONTRACTILITY BY PLANT-DERIVED SESQUITERPENES CAUSED BY THEIR CHEMICALLY REACTIVE ALPHA-METHYLENEBUTYROLACTONE FUNCTIONS
Ajb. Hay et al., TOXIC INHIBITION OF SMOOTH-MUSCLE CONTRACTILITY BY PLANT-DERIVED SESQUITERPENES CAUSED BY THEIR CHEMICALLY REACTIVE ALPHA-METHYLENEBUTYROLACTONE FUNCTIONS, British Journal of Pharmacology, 112(1), 1994, pp. 9-12
1 Previous studies have shown that extracts of feverfew (Tanacetum par
thenium) and parthenolide, a sesquiterpene alpha-methylenebutyrolacton
e obtained from it, inhibit smooth muscle contractility in a time-depe
ndent, non-specific and irreversible manner. 2 The hypothesis that thi
s toxic effect is due specifically to the presence in the sesquiterpen
e lactone of the potentially reactive alpha-methylene function was tes
ted on rabbit isolated aortic ring preparations. This was done (a) by
comparing the effects of two plant-derived sesquiterpene lactones puri
fied from yellow star thistle (Centaurea solstitialis): cynaropicrin (
an alpha-methylenebutyrolactone) and solstitialin 13-acetate (lacking
the alpha-methylene function), and (b) by chemically inactivating the
alpha-methylene functions in cynaropicrin and parthenolide by reaction
with cysteine. 3 The results show that the characteristic smooth musc
le inhibitory profile is demonstrated by the two alpha-methylenebutyro
lactones (parthenolide and cynaropicrin), but not by the compound lack
ing this functional group (solstitialin 13-acetate), or by those previ
ously active compounds in which it has been inactivated with cysteine.
4 Thus the alpha-methylene function is critical for this aspect of th
e toxic pharmacological profile of the sesquiterpene butyrolactones, w
hich are natural products widely distributed in the Compositae family
of flowering plants.