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

Loredana Serpe; Silvano Ellena; Nadia Barbero; Federica Foglietta; Federica Prandini; Maria Pia Gallo; Renzo Levi; Claudia Barolo; Roberto Canaparo; Sonja Visentin

doi:10.1016/j.ejmech.2016.02.035

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.

Authors

Affiliations

¹ University of Torino, Department of Drug Science and Technology, Via Pietro Giuria 13, 10125 Torino, Italy.
² University of Torino, Department of Chemistry and NIS Interdepartmental Centre, Via Pietro Giuria 7, 10125 Torino, Italy.
³ University of Torino, Department of Chemistry and NIS Interdepartmental Centre, Via Pietro Giuria 7, 10125 Torino, Italy. Electronic address: nadia.barbero@unito.it.
⁴ University of Torino, Department of Life Sciences and Systems Biology, Via Accademia Albertina 13, 10123 Torino, Italy.
⁵ University of Torino, Department of Molecular Biotechnology and Health Science, Via Quarello15, 10135 Torino, Italy.

PMID: 26942626
DOI: 10.1016/j.ejmech.2016.02.035

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