Bromo- and glycosyl-substituted BODIPYs for application in photodynamic therapy and imaging

Org Biomol Chem. 2023 Apr 12;21(15):3105-3120. doi: 10.1039/d2ob02174a.

Abstract

The introduction of heavy atoms into the BODIPY-core structure has proven to be a straightforward strategy for optimizing the design of such dyes towards enhanced generation of singlet oxygen rendering them suitable as photosensitizers for photodynamic therapy (PDT). In this work, BODIPYs are presented by combining the concept of bromination with nucleophilic aromatic substitution (SNAr) of a pentafluorophenyl or a 4-fluoro-3-nitrophenyl moiety to introduce functional groups, thus improving the phototoxic effect of the BODIPYs as well as their solubility in the biological environment. The nucleophilic substitution enabled functionalization with various amines and alcohols as well as unprotected thiocarbohydrates. The phototoxic activity of these more than 50 BODIPYs has been assessed in cellular assays against four cancer cell lines in order to more broadly evaluate their PDT potential, thus accounting for the known variability between cell lines with respect to PDT activity. In these investigations, dibrominated polar-substituted BODIPYs, particularly dibrominated glyco-substituted compounds, showed promising potential as photomedicine candidates. Furthermore, the cellular uptake of the glycosylated BODIPYs has been confirmed via fluorescence microscopy.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Boron Compounds / chemistry
  • Cell Line
  • Photochemotherapy*
  • Photosensitizing Agents* / chemistry

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Photosensitizing Agents
  • Boron Compounds