Squaraines bearing halogenated moieties as anticancer photosensitizers: Synthesis, characterization and biological evaluation

Eur J Med Chem. 2016 May 4:113:187-97. doi: 10.1016/j.ejmech.2016.02.035. Epub 2016 Feb 20.

Abstract

We report the synthesis and characterization of a series of symmetrical indolenine-based squaraine dyes along with the evaluation of their singlet oxygen generation efficiency. The photodynamic activity of these new photosensitizers has been evaluated on a human tumor fibrosarcoma (HT-1080) cell line. The cytotoxicity increased over time and is induced by the photoactivation of bromo (Br-C4) and iodio (I-C4) long carbon chain squaraine dyes and the consequent increase in reactive oxygen species (ROS) production (p < 0.001), which leads to necrosis 6 h after treatment. Induction of cytochrome c release, DNA damage and up-regulation of GPX1, NQO1 and SOD2 mRNA gene expression after PDT were investigated.

Keywords: Cancer; Photodynamic therapy; Photosensitizers; Singlet oxygen; Squaraines.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Death / drug effects
  • Cell Proliferation / drug effects
  • Cyclobutanes / chemical synthesis
  • Cyclobutanes / chemistry
  • Cyclobutanes / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Halogens / chemistry*
  • Humans
  • Models, Molecular
  • Molecular Structure
  • Phenols / chemical synthesis
  • Phenols / chemistry
  • Phenols / pharmacology*
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship
  • Tumor Cells, Cultured

Substances

  • Antineoplastic Agents
  • Cyclobutanes
  • Halogens
  • Phenols
  • Photosensitizing Agents
  • Reactive Oxygen Species
  • squaraine