Discovery of natural products from Curcuma longa that protect cells from beta-amyloid insult: a drug discovery effort against Alzheimer's disease

J Nat Prod. 2002 Sep;65(9):1227-31. doi: 10.1021/np010039x.

Abstract

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).

MeSH terms

  • Alzheimer Disease / physiopathology*
  • Amyloid beta-Peptides / pharmacology*
  • Amyloid beta-Peptides / toxicity
  • Animals
  • Biological Products / chemistry
  • Biological Products / isolation & purification*
  • Biological Products / pharmacology
  • Cell Survival / drug effects
  • Cell Survival / physiology
  • Cinnamates
  • Curcuma / chemistry*
  • Curcumin / analogs & derivatives*
  • Curcumin / chemistry
  • Curcumin / isolation & purification*
  • Curcumin / pharmacology*
  • Diarylheptanoids
  • Diterpenes / chemistry
  • Diterpenes / isolation & purification*
  • Diterpenes / pharmacology
  • Molecular Structure
  • Monoterpenes
  • PC12 Cells / drug effects
  • Peptide Fragments
  • Plants, Medicinal / chemistry*
  • Rats

Substances

  • 1,7-bis(4-hydroxy-3-methoxyphenyl)-1,4,6-heptatrien-3-one
  • 1,7-bis(4-hydroxyphenyl)-1-heptene-3,5-dione
  • Amyloid beta-Peptides
  • Biological Products
  • Cinnamates
  • Diarylheptanoids
  • Diterpenes
  • Monoterpenes
  • Peptide Fragments
  • amyloid beta-protein (1-42)
  • amyloid beta-protein (25-35)
  • calebin-A
  • kansuinin B
  • kansuinin C
  • bisdemethoxycurcumin
  • Curcumin
  • demethoxycurcumin