Total synthesis of Calebin-A, preparation of its analogues, and their neuronal cell protectivity against beta-amyloid insult

Bioorg Med Chem Lett. 2001 Sep 17;11(18):2541-3. doi: 10.1016/s0960-894x(01)00489-9.

Abstract

A total synthesis of Calebin-A (1), a novel curcuminoid isolated from turmeric (Curcuma longa, Zingiberaceae) that has been demonstrated to protect neuronal cells from beta-amyloid insult, was successfully achieved in four steps. Elaborating on this synthetic route, 13 analogues were prepared for a structure-activity relationship (SAR) study. It was found that the parent compound 1 and derivatives 21, 28, and 30 protect PC12 rat pheocromocytoma and IMR-32 human neuroblastoma cells from beta-amyloid(25-35) insult. These results suggest that hydroxy group at para-position is most critical for the expression of biological activity.

MeSH terms

  • Amyloid beta-Peptides / toxicity*
  • Animals
  • Biochemistry / methods
  • Cinnamates
  • Curcumin / analogs & derivatives
  • Curcumin / pharmacology*
  • Dose-Response Relationship, Drug
  • Humans
  • Magnetic Resonance Spectroscopy
  • Monoterpenes
  • Neuroprotective Agents / chemistry*
  • Neuroprotective Agents / pharmacology*
  • Peptide Fragments / toxicity*
  • Rats
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Amyloid beta-Peptides
  • Cinnamates
  • Monoterpenes
  • Neuroprotective Agents
  • Peptide Fragments
  • amyloid beta-protein (25-35)
  • calebin-A
  • Curcumin