Synthesis and evaluation of macrocyclic diarylether heptanoid natural products and their analogs

Bioorg Med Chem Lett. 2012 Jan 1;22(1):245-8. doi: 10.1016/j.bmcl.2011.11.025. Epub 2011 Nov 11.

Abstract

The macrocyclic diarylether heptanoid (MDEH) natural products have been used in folk medicine for centuries. MDEHs are reported to exert anti-tumor properties by inhibiting the activation of NF-κB. Here we report the synthesis of a small MDEH library (first reported synthesis of racemic platycarynol) using a Grubbs cross metathesis/Ullmann cyclization strategy. Evaluation of the library led to the identification of MDEH 9b which sensitizes pancreatic cancer cells to gemcitabine mediated growth inhibition and apoptosis.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Antineoplastic Agents / pharmacology
  • Apoptosis
  • Biological Products / chemistry
  • Biological Products / pharmacology
  • Cell Line
  • Chemistry, Pharmaceutical / methods
  • Drug Design
  • Ether / analogs & derivatives*
  • HEK293 Cells
  • Humans
  • Models, Chemical
  • NF-kappa B / metabolism
  • Pancreatic Neoplasms / drug therapy*
  • Time Factors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Antineoplastic Agents
  • Biological Products
  • NF-kappa B
  • Tumor Necrosis Factor-alpha
  • Ether