ABSTRACT
One novel lavandulyl flavanone (=2,3-dihydro-2-phenyl-4H-1-benzopyran-4-one) with an unusual 5,2',4',6'-tetrahydroxy substitution, calycinigin A (1), was isolated from the stems of Hypericum calycinum L. (Hypericaceae). The structure was elucidated on the basis of 1D- and 2D-NMR analysis, as well as mass spectrometry (LR-EI- and HR-EI-MS) and circular dichroism. Three known lavandulyl flavanones with 5,7,2',4',6'-pentahydroxy substitution, i.e., 2-4, were also isolated. Chemosystematically, this is the first report on the occurrence of prenylated flavanones in the family Hypericaceae. Reduction of cell viability by all compounds was evaluated in a MTT (=3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl-2H-tetrazolium bromide) assay using HeLa cells. Compound 1 showed moderate activity with an IC50 value of 9.7±1.8â µM, whereas compounds 2-4 were less active exhibiting IC50 values of 11.6±0.9, 19.3±1.5, and 40.7±2.4â µM, respectively. The antioxidant activity was evaluated by an ORAC (Oxygen Radical Absorbance Capacity) assay, and calycinigin A (1) was again the most active compound with a Trolox equivalent of 2.3±0.2. None of the compounds was able to reduce the TNF-α induced ICAM-1 expression in vitro using human microvascular endothelial cells (HMEC-1).
Subject(s)
Flavanones/chemistry , Hypericum/chemistry , Antioxidants/chemistry , Antioxidants/isolation & purification , Cell Line , Cell Survival/drug effects , Endothelial Cells/drug effects , Endothelial Cells/metabolism , Flavanones/isolation & purification , Flavanones/pharmacology , Flavanones/toxicity , Free Radicals/chemistry , HeLa Cells , Humans , Intercellular Adhesion Molecule-1/metabolism , Magnetic Resonance Spectroscopy , Mass Spectrometry , Molecular Conformation , Plant Stems/chemistry , Tumor Necrosis Factor-alpha/pharmacologyABSTRACT
Three new steroid saponins (3beta,25R)-spirost-5-en-3-yl 6-deoxy-alpha-L-mannopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)-6-deoxy-alpha-L-mannopyranosyl-(1-->3)]-beta-D-glucopyranoside (1), (3beta,22R,25R)-26-(beta-D-glucopyranosyloxy)-22-hydroxyfurost-5-en-3-yl 6-deoxy-alpha-L-mannopyranosyl-(1-->2)-[6-deoxy-alpha-L-mannopyranosyl-(1-->3)]-beta-D-glucopyranoside (3), and (3beta,22R,25R)-26-(beta-D-glucopyranosyloxy)-22-hydroxyfurost-5-en-3-yl 6-deoxy-alpha-L-mannopyranosyl-(1-->2)-[beta-D-glucopyranosyl-(1-->4)-6-deoxy-alpha-L-mannopyranosyl-(1-->3)]-beta-D-glucopyranoside (5), as well as the new pregnane glycoside (3beta,16beta)-3-{[6-deoxy-alpha-L-mannopyranosyl-(1-->2)-[6-deoxy-alpha-L-mannopyranosyl-(1-->3)]-beta-D-glucopyranosyl]oxy}-20-oxopregn-5-en-16-yl (4R)-5-(beta-D-glucopyranosyloxy)-4-methylpentanoate (6), were isolated from the rhizomes of Tacca integrifolia together with two known (25R) configurated steroid saponins (3beta,25R)-spirost-5-en-3-yl 6-deoxy-alpha-L-mannopyranosyl-(1-->2)-[6-deoxy-alpha-L-mannopyranosyl-(1-->3)]-beta-D-glucopyranoside (2) and (3beta,22R,25R)-26-(beta-D-glucopyranosyloxy)-22-methoxyfurost-5-en-3-yl 6-deoxy-alpha-L-mannopyranosyl-(1-->2)-[6-deoxy-alpha-L-mannopyranosyl-(1-->3)]-beta-D-glucopyranoside (4). The cytotoxic activity of the isolated compounds was evaluated in HeLa cells and showed the highest cytotoxicity value for compound 2 with an IC(50) of 1.2+/-0.4 muM. Intriguingly, while compounds 1-5 exhibited similar cytotoxic properties between 1.2+/-0.4 (2) and 4.0+/-0.6 muM (5), only compound 2 showed a significant microtubule-stabilizing activity in vitro.
