Synthesis and biological profiling of parthenolide ether analogs

Org Biomol Chem. 2019 Dec 7;17(45):9703-9707. doi: 10.1039/c9ob02166c. Epub 2019 Nov 8.

Abstract

Parthenolide (PTL) strongly inhibits the detyrosination of microtubules and accelerates neuronal growth. In order to access cyclic ether derivatives of PTL, ring-closing metathesis (RCM) was investigated in comparison to intramolecular sulfone alkylation. Incompatibility of RCM with epoxides was found in this setting. Biological evaluation for tubulin carboxypeptidase inhibition indicated that the epoxide is crucial for parthenolide's activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Carboxypeptidases / antagonists & inhibitors*
  • Carboxypeptidases / metabolism
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Ether / chemical synthesis
  • Ether / chemistry
  • Ether / pharmacology*
  • Humans
  • Microtubules / drug effects*
  • Molecular Structure
  • Neurons / drug effects*
  • Sesquiterpenes / chemical synthesis
  • Sesquiterpenes / chemistry
  • Sesquiterpenes / pharmacology*
  • Structure-Activity Relationship
  • Tanacetum parthenium / chemistry

Substances

  • Enzyme Inhibitors
  • Sesquiterpenes
  • Ether
  • parthenolide
  • Carboxypeptidases
  • tyrosyltubulin carboxypeptidase