G.B Elyakov Pacific Institute of Bioorganic
Chemistry, Far Eastern Branch, Russian Academy of Sciences, Pr. 100-let
Vladivostoku 159, Vladivostok, Russian Federation
Abstract
Seven
eremophilane-type sesquiterpenes (1-7), six cycloartane derivatives
(8-13) and α-amyrin acetate (14) were isolated from the leaves of the
far-eastern plant Ligularia
alticola Worosch. (Family Asteraceae).
(4S,5R,8S,10R)-8-Ethoxyeremophil-7(11)-en-12(8)-olide (1),
8α,11-epidioxy-8β-methoxyeremophil-6-ene (2) and 29-norcycloartan-3α-ol
(8) have not been previously reported. Fukinone α-epoxide (3) was
isolated for the first time from a natural source. The structures of all
the compounds were established by the extensive analysis of their 1D
and 2D NMR spectra and HR ESI mass spectrometry. The absolute
stereochemistry of 1 was determined by comparison of theoretical and
experimental ECD spectra with the application of B3LYP-TDDFT and
B3LYP-GIAO calculations as well as by NMR spectroscopy. Compound 1
showed cytotoxic action against human cancer HL-60, Raji, and THP-1 cell
lines (IC50 12.6, 6.0 and 6.9 μM, respectively). Compounds 2 and 4 demonstrated significant cytotoxic activities against HL-60 (IC50 2.8 and 5.8 μM, respectively) and Raji cells (IC50 2.9 and 4.2 μM, respectively). Compound 6 was cytotoxic against Raji cells (IC50
4.6 μM). None of tested compounds were cytotoxic against RAW 264.7
cells. Compounds 1 and 4-7 significantly decreased intracellular ROS
levels, induced by endotoxic LPS from Escherichia coli in RAW 264.7
murine macrophages. © 2015 Elsevier Ltd.
Author keywords
4 14-Dimethylsteroids; Anti-inflammatory activity; B3LYP; Cytotoxicity; Eremophilane-type sesquiterpenes; Ligularia alticola
Indexed keywords
EMTREE drug terms: 29 norcycloartan 3 alpha ol; 7,8
dihydroxybenzo[a]pyrene 9,10 oxide; 8 alpha,11 epidioxy 8 beta
methoxyeremophil 6 ene; 8 ethoxyeremophil 7(11) en 12(8) olide; alpha
amyrin; cytotoxic agent; fukinone alpha epoxide; lipopolysaccharide;
reactive oxygen metabolite; sesquiterpene; unclassified drug
EMTREE medical terms: animal cell; Article; biological
activity; cancer cell line; cell level; cytotoxicity; drug cytotoxicity;
drug isolation; Escherichia coli; human; human cell; IC50; Ligularia
alticola; macrophage; mass spectrometry; medicinal plant; nonhuman; nuclear magnetic resonance; plant leaf; priority journal; Raji cell line; stereochemistry
Chemicals and CAS Registry Numbers: alpha amyrin, 638-95-9
