The first metal-based paullone derivative with high antiproliferative activity in vitro

Inorg Chem. 2006 Mar 6;45(5):1945-50. doi: 10.1021/ic0511120.

Abstract

9-Bromo-7,12-dihydroindolo[3,2-d][1]benzazepin-6(5H)-one, kenpaullone, which displays similarities in the activity profile to flavopiridol, was modified by chemical transformations at the lactam unit to provide a peripheral binding site able to accommodate metal ions. The first metal-based paullone has been prepared and characterized by single-crystal X-ray diffraction methods, solid-state cross-polarization magic angle spinning 13C NMR spectroscopy, electrospray ionization mass spectra, and electronic spectra. The gallium complex [GaL2]Cl.2.5H2O, the metal-free ligand (HL), and the starting compound used for the preparation of HL were assessed in vitro for their cytotoxicity in a panel of human tumor cell lines. The gallium complex was found to be 1.5-18-fold more cytotoxic than HL, with an average IC50 value of 2.0 microM.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Crystallography, X-Ray
  • Drug Screening Assays, Antitumor
  • Flavonoids / chemistry
  • Galium / chemistry
  • Humans
  • Ligands
  • Magnetic Resonance Spectroscopy
  • Metals / chemistry
  • Molecular Structure
  • Piperidines / chemistry
  • Spectrometry, Mass, Electrospray Ionization
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Flavonoids
  • Ligands
  • Metals
  • Piperidines
  • alvocidib