Hexylitaconic acid: a new inhibitor of p53-HDM2 interaction isolated from a marine-derived fungus, Arthrinium sp

Bioorg Med Chem Lett. 2006 Jan 1;16(1):69-71. doi: 10.1016/j.bmcl.2005.09.052. Epub 2005 Oct 21.

Abstract

A new inhibitor of p53-HDM2 interaction was isolated from a culture of marine-derived fungus, Arthrinium sp. The structure was identified to be (-)-hexylitaconic acid (1) by spectroscopic analysis. The inhibition of p53-HDM2 binding was tested by the ELISA method, and 1 inhibited the binding with an IC(50) value of 50 microg/mL. Although a number of synthetic inhibitors of p53-HDM2 interaction have been reported so far, 1 is the second inhibitor isolated from natural resources.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Ascomycota / metabolism*
  • Chemistry, Pharmaceutical / methods*
  • Crystallography, X-Ray
  • Dose-Response Relationship, Drug
  • Drug Design*
  • Enzyme Inhibitors / pharmacology*
  • Enzyme-Linked Immunosorbent Assay
  • Fungal Proteins / chemistry
  • Humans
  • Inhibitory Concentration 50
  • Models, Chemical
  • Protein Binding
  • Proto-Oncogene Proteins c-mdm2 / metabolism*
  • Succinates / chemistry*
  • Tumor Suppressor Protein p53 / chemistry*
  • Tumor Suppressor Protein p53 / metabolism

Substances

  • 2-methylene-3-hexylbutanedioic acid
  • Enzyme Inhibitors
  • Fungal Proteins
  • Succinates
  • Tumor Suppressor Protein p53
  • MDM2 protein, human
  • Proto-Oncogene Proteins c-mdm2