Restricted suitability of BODIPY for caging in biological applications based on singlet oxygen generation

Photochem Photobiol Sci. 2020 Oct 14;19(10):1319-1325. doi: 10.1039/d0pp00097c.

Abstract

Recent studies report the boron-dipyrromethene (BODIPY) moiety to be interesting for caging applications in photopharmacology based on its response to irradiation with wavelengths in the biooptical window. Thus, in a model study, we investigated the meso-methyl-BODIPY caged CDK2 inhibitor AZD5438 and aimed to assess the usability of BODIPY as a photoremovable protecting group in photoresponsive kinase inhibitor applications. Photochemical analysis and biological characterisation in vitro revealed significant limitations of the BODIPY-caged inhibitor concept regarding solubility and uncaging in aqueous solution. Notably, we provide evidence for BODIPY-caged compounds generating singlet oxygen/radicals upon irradiation, followed by photodegradation of the caged compound system. Consequently, instead of caging, a non-specific induction of necrosis in cells suggests the potential usage of BODIPY derivatives for photodynamic approaches.

MeSH terms

  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology*
  • Cyclin-Dependent Kinase 2 / antagonists & inhibitors*
  • Cyclin-Dependent Kinase 2 / metabolism
  • Humans
  • Imidazoles / chemical synthesis
  • Imidazoles / chemistry
  • Imidazoles / pharmacology
  • Ligands
  • Models, Molecular
  • Molecular Structure
  • Protein Kinase Inhibitors / chemical synthesis
  • Protein Kinase Inhibitors / chemistry
  • Protein Kinase Inhibitors / pharmacology
  • Pyrimidines / chemical synthesis
  • Pyrimidines / chemistry
  • Pyrimidines / pharmacology
  • Singlet Oxygen / chemistry
  • Singlet Oxygen / metabolism*

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Boron Compounds
  • Imidazoles
  • Ligands
  • Protein Kinase Inhibitors
  • Pyrimidines
  • Singlet Oxygen
  • AZD5438
  • CDK2 protein, human
  • Cyclin-Dependent Kinase 2