On the synthesis of quinone-based BODIPY hybrids: New insights on antitumor activity and mechanism of action in cancer cells

Bioorg Med Chem Lett. 2017 Sep 15;27(18):4446-4456. doi: 10.1016/j.bmcl.2017.08.007. Epub 2017 Aug 4.

Abstract

Fluorescent quinone-based BODIPY hybrids were synthesised and characterised by NMR analysis and mass spectrometry. We measured their cytotoxic activity against cancer and normal cell lines, performed mechanistic studies by lipid peroxidation and determination of reduced (GSH) and oxidized (GSSG) glutathione, and imaged their subcellular localisation by confocal microscopy. Cell imaging experiments indicated that nor-β-lapachone-based BODIPY derivatives might preferentially localise in the lysosomes of cancer cells. These results assert the potential of hybrid quinone-BODIPY derivatives as promising prototypes in the search of new potent lapachone antitumor drugs.

Keywords: BODIPY; Cancer; Lapachone; Quinone; Subcellular localization.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzoquinones / chemical synthesis
  • Benzoquinones / chemistry
  • Benzoquinones / pharmacology*
  • Boron Compounds / chemistry
  • Boron Compounds / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Molecular Structure
  • Structure-Activity Relationship

Substances

  • 4,4-difluoro-4-bora-3a,4a-diaza-s-indacene
  • Antineoplastic Agents
  • Benzoquinones
  • Boron Compounds
  • quinone