Antiproliferative agents that interfere with the cell cycle at the G1-->S transition: further development and characterization of a small library of stilbene-derived compounds

ChemMedChem. 2008 Feb;3(2):345-55. doi: 10.1002/cmdc.200700258.

Abstract

In this continuation of our research on derivatives containing the stilbene privileged structure or that are derived from it, we report the results of further studies carried out on the previously initiated collection of compounds. We used a parallel synthetic approach to rapidly obtain small sets of compounds and started the annotation of the library in progress by calculating some physicochemical properties to be eventually correlated with biological activities. A pharmacophore for the antiproliferative activity was also built to summarize the features of the library. We evaluated the antiproliferative and pro-apoptotic activities of all compounds as well as the cell-cycle effects of some representative compounds. After in-depth investigations, 3'-phenyl-[1,1';4',1'']terphenyl-4,3'',5''-triol showed the most interesting biological profile, as it interferes with cell-cycle progression at the G(1)-->S transition, acting on retinoblastoma phosphorylation and inducing cell differentiation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Apoptosis / physiology
  • Cell Differentiation / drug effects*
  • Cell Differentiation / physiology
  • Cell Line, Tumor
  • Flow Cytometry
  • G1 Phase / drug effects*
  • G1 Phase / physiology
  • HL-60 Cells
  • Humans
  • Inhibitory Concentration 50
  • K562 Cells
  • Phosphorylation
  • Retinoblastoma / chemistry
  • Retinoblastoma / metabolism
  • S Phase / drug effects*
  • S Phase / physiology
  • Small Molecule Libraries / chemical synthesis
  • Small Molecule Libraries / pharmacology*
  • Stilbenes / chemical synthesis
  • Stilbenes / pharmacology*

Substances

  • Antineoplastic Agents
  • Small Molecule Libraries
  • Stilbenes