Semisynthesis and biological evaluation of a cotylenin A mimic derived from fusicoccin A

Bioorg Med Chem Lett. 2018 Feb 15;28(4):646-650. doi: 10.1016/j.bmcl.2018.01.030.

Abstract

In an effort to overcome the unavailability of cotylenin A (CN A), an anticancer agent and a stabilizer of protein-protein interactions (PPIs) mediated by 14-3-3 proteins, ISIR-050 was designed as a CN A mimic. The synthesis was accomplished via a semisynthetic approach starting from fusicoccin A. ISIR-050 showed interferon-α (IFNα)-dependent growth inhibitory activity and a PPI stabilization effect similar to those of CN A. The biochemical analysis suggested that ISIR-050 and CN A induce the same pharmacological response to IFNα-treated cancer cells and that 14-3-3 proteins play a role in the mode of action.

Keywords: 14-3-3 Protein; Anticancer agent; Cotylenin; Fusicoccin; Protein–protein interaction.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 14-3-3 Proteins / metabolism
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Line, Tumor
  • Diterpenes / chemical synthesis
  • Diterpenes / chemistry
  • Diterpenes / pharmacology*
  • Glycosides / chemical synthesis
  • Glycosides / chemistry
  • Glycosides / pharmacology*
  • Humans
  • Molecular Structure
  • Protein Stability
  • Stereoisomerism
  • Structure-Activity Relationship

Substances

  • 14-3-3 Proteins
  • Antineoplastic Agents
  • Diterpenes
  • Glycosides
  • cotylenin A
  • fusicoccin