Abstract:
In a bioassay guided search for antimycobacterial compounds from higher
plants, the root extracts of Elecampane (Inula helenium L.; Asteraceae) and Sweet Coneflower (Rudbeckia
subtomentosa Pursh.; Asteraceae) were chemically investigated for their
active constituents. Chromatographic fractions of root extracts of
I. helenium, which exhibited significant activity against Mycobacterium tuberculosis, provided the known eudesmanolides
alantolactone, isoalantolactone, and 11αH,13-dihydroisoalantolactone.
Peracid epoxidation of alantolactone and isoalantolactone provided 5α-epoxyalantolactone
and 4(15)α-epoxyisoalantolactone, respectively and oxidation of alantolactone
with OsO4 gave 11,13-dihydroxyalantolactone. Active
fractions from R. subtomentosa contained the
known allo-alantolactone and 3-oxoalloalantolactone. The structures of the
above compounds were established by spectroscopic methods including 1D and
2D NMR techniques as well as spectral comparison with previously reported
data. The molecular structure of 5α-epoxyalantolactone was determined
by single crystal X-ray diffraction. Eleven natural and semisynthetic eudesmanolides
were tested in a radiorespirometric bioassay for activity against
M. tuberculosis. 5α-Epoxyalantolactone and encelin from Montanoa speciosa showed minimum inhibitory concentrations
(MICs) of 8 and 16 μg ml-1, respectively. Alantolactone,
isoalantolactone and its 4α,15-epoxide, 1,2-dehydro-3-epi-isotelekin and
alloalantolactone gave MICs of 32 μg ml-1. All
other compounds showed MIC values of 128 μg ml-1
or higher.
Key words:
Inula helenium
-
Rudbeckia subtomentosa
-
R. mollis
-
Montanoa speciosa
- Asteraceae - sesquiterpene lactones - eudesmanolides -
Mycobacterium tuberculosis
- antituberculosis activity
