Synthesis, spectroscopic studies and biological evaluation of acridine derivatives: The role of aggregation on the photodynamic efficiency

Bioorg Med Chem Lett. 2018 Mar 1;28(5):869-874. doi: 10.1016/j.bmcl.2018.02.005. Epub 2018 Feb 3.

Abstract

Two new photoactive compounds (1 and 2) derived from the 9-amidoacridine chromophore have been synthesized and fully characterized. Their abilities to produce singlet oxygen upon irradiation have been compared. The synthesized compounds show very different self-aggregating properties since only 1 present a strong tendency to aggregate in water. Biological assays were conducted with two cell types: hepatoma cells (Hep3B) and human umbilical vein endothelial cells (HUVEC). Photodynamic therapy (PDT) studies carried out with Hep3B cells showed that non-aggregating compound 2 showed photoxicity, ascribed to the production of singlet oxygen, being aggregating compound 1 photochemically inactive. On the other hand suspensions of 1, characterized as nano-sized aggregates, have notable antiproliferative activity towards this cell line in the dark.

Keywords: 9-Amidoacridine; Organic nanoparticles; Photodynamic therapy; Self-aggregation; Singlet oxygen.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Acridines / chemical synthesis
  • Acridines / chemistry
  • Acridines / pharmacology*
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Human Umbilical Vein Endothelial Cells / drug effects
  • Humans
  • Microscopy, Fluorescence
  • Molecular Structure
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Structure-Activity Relationship
  • Ultraviolet Rays

Substances

  • Acridines
  • Photosensitizing Agents