Phenylethanoid glycosides from Digitalis purpurea and Penstemon linarioides with PKCalpha-inhibitory activity.
In a continuation of our search for potential tumor inhibitors from plants, it was found that the CH2Cl2-MeOH (1:1) extracts from Digitalis purpurea and Penstemon linarioides both showed PKCalpha-inhibitory bioactivity. Bioassay-directed fractionation of the extract from D. purpurea yielded the new, weakly active phenylethanoid glycoside 2-(3-hydroxy-4-methoxy-phenyl)-ethyl-O-(alpha-L-rhamnosyl)-(1-->3) -O- (alpha-L-rhamnosyl)-(1-->6)-4-O-E-feruloyl-beta-D-glucopy ran oside (1) together with the four known compounds calceolarioside A (2), calceolarioside B (3), forsythiaside (4), and plantainoside D (5). The extract from P. linarioides yielded the three known glycosides leucosceptoside A (6), acteoside (7), and poliumoside (8), together with the iridoid plantarenaloside (9). All of the isolated compounds, except compound 9, showed inhibitory activity against PKCalpha with IC50 values (in microM) of 125 (1), 0.6 (2), 4.6 (3), 1.9 (4), 14.8 (5), 19.0 (6), 9.3 (7), and 24.4 (8).
Zhou
B N
BN
Department of Chemistry, Virginia Polytechnic Institute and State University, Blacksburg, Virginia 24061-0212, USA.
Bahler
B D
BD
Hofmann
G A
GA
Mattern
M R
MR
Johnson
R K
RK
Kingston
D G
DG
D002109:Caffeic Acids / Q000302:isolation & purification* / Q000494:pharmacology; D004070:Digitalis / Q000737:chemistry*; D004791:Enzyme Inhibitors / Q000302:isolation & purification* / Q000494:pharmacology; D006027:Glycosides / Q000302:isolation & purification* / Q000494:pharmacology; D006801:Humans; D007527:Isoenzymes / Q000037:antagonists & inhibitors*; D009682:Magnetic Resonance Spectroscopy; D010946:Plants, Medicinal / Q000737:chemistry*; D010947:Plants, Toxic; D011493:Protein Kinase C / Q000037:antagonists & inhibitors*; D051571:Protein Kinase C-alpha; D016339:Spectrometry, Mass, Fast Atom Bombardment; D013055:Spectrophotometry, Infrared; D013056:Spectrophotometry, Ultraviolet
D002109:Caffeic Acids; D004791:Enzyme Inhibitors; D006027:Glycosides; D007527:Isoenzymes; C584242:poliumoside; C496628:PRKCA protein, human; D011493:Protein Kinase C; D051571:Protein Kinase C-alpha