Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's disease.
From Curcuma longa, two novel compounds, 4' '-(3' "-methoxy-4' "-hydroxyphenyl)-2' '-oxo-3' '-enebutanyl 3-(3'-methoxy-4'hydroxyphenyl)propenoate (calebin-A, 1) and 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one (2), and seven known compounds, 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,6-heptadiene-3,5-dione (curcumin, 3), 1-(4-hydroxy-3-methoxyphenyl)-7-(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (demethoxycurcumin, 4), 1,7-bis(4-hydroxyphenyl)-1,6-heptadiene-3,5-dione (bisdemethoxycurcumin, 5), 1-hydroxy-1,7-bis(4-hydroxy-3-methoxyphenyl)-6-heptene-3,5-dione (6), 1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione (7), 1,7-bis(4-hydroxyphenyl)-1,4,6-heptatrien-3-one (8), and 1,5-bis(4-hydroxy-3-methoxyphenyl)-1,4-pentadien-3-one (9), were isolated following a bioassay-guided fractionation scheme utilizing an assay to detect protection of PC12 cells from beta-amyloid insult. Compounds 1, 3-5, and 7 were found to more effectively protect PC12 cells from betaA insult (ED(50) = 0.5-10 microg/mL) than Congo red (10) (ED(50) = 37-39 microg/mL).
D000544:Alzheimer Disease / Q000503:physiopathology*; D016229:Amyloid beta-Peptides / Q000494:pharmacology* / Q000633:toxicity; D000818:Animals; D001688:Biological Products / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D002470:Cell Survival / Q000187:drug effects / Q000502:physiology; D002934:Cinnamates; D030024:Curcuma / Q000737:chemistry*; D003474:Curcumin / Q000031:analogs & derivatives* / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology*; D036381:Diarylheptanoids; D004224:Diterpenes / Q000737:chemistry / Q000302:isolation & purification* / Q000494:pharmacology; D015394:Molecular Structure; D039821:Monoterpenes; D016716:PC12 Cells / Q000187:drug effects; D010446:Peptide Fragments; D010946:Plants, Medicinal / Q000737:chemistry*; D051381:Rats
D016229:Amyloid beta-Peptides; D001688:Biological Products; D002934:Cinnamates; D003474:Curcumin; D036381:Diarylheptanoids; D004224:Diterpenes; D039821:Monoterpenes; D010446:Peptide Fragments; C471106:ASC-J9 compound; C470147:1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione; C075222:amyloid beta-protein (1-42); C074636:amyloid beta-protein (25-35); C448819:calebin-A; C470413:kansuinin B; C470414:kansuinin C; C034786:bisdemethoxycurcumin; C050229:demethoxycurcumin