A novel metal-chelating inhibitor of protein farnesyltransferase

Bioorg Med Chem Lett. 2003 May 5;13(9):1523-6. doi: 10.1016/s0960-894x(03)00183-5.

Abstract

A novel metal chelator comprising a 4-(naphthalen-1-yl)pyridine and 2-aminoethanethiol was synthesized. This showed inhibitory activity against human protein farnesyltransferase with IC(50) 1.9 microM, induced morphological change in K-ras-NRK cells at 0.5 microg/mL and showed growth inhibition of K-ras-NRK cells with IC(50) 0.32 microg/mL.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Alkyl and Aryl Transferases / antagonists & inhibitors*
  • Alkyl and Aryl Transferases / chemistry*
  • Animals
  • Cell Division / drug effects
  • Cell Line
  • Chelating Agents / chemical synthesis*
  • Chelating Agents / chemistry
  • Chelating Agents / pharmacology
  • Chlorides / chemistry
  • Enzyme Inhibitors / chemical synthesis*
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology
  • Genes, ras / drug effects
  • Humans
  • Naphthalenes / chemical synthesis*
  • Naphthalenes / chemistry
  • Naphthalenes / pharmacology
  • Pyridines / chemical synthesis*
  • Pyridines / chemistry
  • Pyridines / pharmacology
  • Rats
  • Structure-Activity Relationship
  • Zinc Compounds / chemistry

Substances

  • Chelating Agents
  • Chlorides
  • Enzyme Inhibitors
  • Naphthalenes
  • Pyridines
  • Zinc Compounds
  • zinc chloride
  • Alkyl and Aryl Transferases
  • p21(ras) farnesyl-protein transferase