Synthesis of the novel elemonic acid derivatives as Pin1 inhibitors

Bioorg Med Chem Lett. 2014 Dec 15;24(24):5612-5615. doi: 10.1016/j.bmcl.2014.10.087. Epub 2014 Nov 1.

Abstract

A novel series of elemonic acid derivatives were synthesized and evaluated for their inhibitory activity on Pin1. Five compounds displayed significantly improved ability to inhibit Pin1 activity at micromolar levels. Compound 10 with 2-carboxylmethylene was the most active one with an IC50 value of 0.57 μM. The docking models of Pin1 support that introduction of an acidic group to elemonic acid enhance the Pin1 inhibitory activity.

Keywords: Anticancer; Elemonic acid; Pin1 inhibition; Tirucallane; Triterpenoid.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Binding Sites
  • Catalytic Domain
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / metabolism
  • Humans
  • Molecular Docking Simulation
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Peptidylprolyl Isomerase / antagonists & inhibitors*
  • Peptidylprolyl Isomerase / metabolism
  • Protein Binding
  • Structure-Activity Relationship
  • Triterpenes / chemical synthesis*
  • Triterpenes / chemistry
  • Triterpenes / metabolism

Substances

  • 3-oxo-tirucall-8,24-dien-21-oic acid
  • Enzyme Inhibitors
  • NIMA-Interacting Peptidylprolyl Isomerase
  • Triterpenes
  • PIN1 protein, human
  • Peptidylprolyl Isomerase