Chemical constituents of Ligularia alticola Worosch. leaves and their biological activities.

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). (4 S ,5 R ,8 S ,10 R )-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 (IC 50 12.6, 6.0 and 6.9 μM, respectively). Compounds 2 and 4 demonstrated significant cytotoxic activities against HL-60 (IC 50 2.8 and 5.8 μM, respectively) and Raji cells (IC 50 2.9 and 4.2 μM, respectively). Compound 6 was cytotoxic against Raji cells (IC 50 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. [ABSTRACT FROM AUTHOR]