Synthesis of analogs of the radiation mitigator JP4-039 and visualization of BODIPY derivatives in mitochondria

Org Biomol Chem. 2013 Jul 7;11(25):4147-53. doi: 10.1039/c3ob40489g.

Abstract

JP4-039 is a lead structure in a series of nitroxide conjugates that are capable of accumulating in mitochondria and scavenging reactive oxygen species (ROS). To explore structure-activity relationships (SAR), new analogs with variable nitroxide moieties were prepared. Furthermore, fluorophore-tagged analogs were synthesized and provided the opportunity for visualization in mitochondria. All analogs were tested for radioprotective and radiomitigative effects in 32Dcl3 cells.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Boron Compounds / analysis*
  • Cell Line
  • Fluorescent Dyes / analysis*
  • Free Radical Scavengers / analysis*
  • Free Radical Scavengers / chemical synthesis
  • Free Radical Scavengers / pharmacology
  • Humans
  • Mitochondria / drug effects
  • Mitochondria / radiation effects
  • Mitochondria / ultrastructure*
  • Models, Molecular
  • Nitrogen Oxides / analysis*
  • Nitrogen Oxides / chemical synthesis
  • Nitrogen Oxides / pharmacology
  • Radiation-Protective Agents / analysis*
  • Radiation-Protective Agents / chemical synthesis
  • Radiation-Protective Agents / pharmacology
  • Radiation-Sensitizing Agents / analysis*
  • Radiation-Sensitizing Agents / chemical synthesis
  • Radiation-Sensitizing Agents / pharmacology

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Fluorescent Dyes
  • Free Radical Scavengers
  • JP4-039
  • Nitrogen Oxides
  • Radiation-Protective Agents
  • Radiation-Sensitizing Agents