6-[1-(2,6-difluorophenyl)ethyl]pyrimidinones antagonize cell proliferation and induce cell differentiation by inhibiting (a nontelomeric) endogenous reverse transcriptase

J Med Chem. 2005 Nov 3;48(22):6776-8. doi: 10.1021/jm0507330.

Abstract

Two 2,6-difluoro-DABO derivatives (MC 1047, 1, and MC 1220, 2, respectively) were tested against endogenous, nontelomeric reverse transcriptase (endo-RT) in human differentiating cell systems to investigate their antiproliferative and cytodifferentiating activity. The two compounds significantly reduced cell proliferation and facilitated the morphological differentiation of cells. These results propose F(2)-DABOs as useful tools in preventive and/or curative therapy to counteract the loss of differentiation in dedifferentiating pathologies and as antiproliferative drugs in tumor therapy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Cell Differentiation / drug effects*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects*
  • Drug Screening Assays, Antitumor
  • Fluorobenzenes
  • Humans
  • Pyrimidinones / chemical synthesis*
  • Pyrimidinones / chemistry
  • Pyrimidinones / pharmacology
  • RNA-Directed DNA Polymerase / metabolism*
  • Reverse Transcriptase Inhibitors / chemical synthesis*
  • Reverse Transcriptase Inhibitors / chemistry
  • Reverse Transcriptase Inhibitors / pharmacology
  • Structure-Activity Relationship

Substances

  • 2-cyclopentylthio-6-(1-(2,6-difluorophenyl)ethyl)-3,4-dihydro-5-methylpyrimidin-4(3H)-one
  • 6-(1-(2,6-difluorophenyl)ethyl)-2-(dimethylamino)-5-methylpyrimidin-4(3H)-one
  • Antineoplastic Agents
  • Fluorobenzenes
  • Pyrimidinones
  • Reverse Transcriptase Inhibitors
  • RNA-Directed DNA Polymerase