Synthesis and biological evaluation of new water-soluble photoactive chlorin conjugate for targeted delivery

Eur J Med Chem. 2018 Jan 20:144:740-750. doi: 10.1016/j.ejmech.2017.12.062. Epub 2017 Dec 19.

Abstract

A new water-soluble conjugate, consisting of a chlorin-based photosensitizing part, and a 4-arylaminoquinazoline moiety with high potential affinity to an epidermal growth factor receptors (EGFR) and vascular endothelial growth factor receptors (VEGFR), suitable for photodynamic therapy (PDT), was synthesized starting from methylpheophorbide-a in seven steps. An increased accumulation of this compound in A431 cells with high level of EGFR expression, in comparison with CHO and HeLa cells with low EGFR expression was observed. The prepared conjugate exhibits dark and photoinduced cytotoxicity at micromolar concentrations with IC50dark/IC50light ratio of 11-18. In tumor-bearing mice, the conjugate preferentially accumulates in the tumor tissue.

Keywords: Chlorins; Conjugate; Medicinal chemistry; PDT; Targeted delivery; Water-solubility.

MeSH terms

  • Animals
  • CHO Cells
  • Cell Line, Tumor
  • Cricetulus
  • Dose-Response Relationship, Drug
  • Drug Delivery Systems*
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Molecular Structure
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Solubility
  • Structure-Activity Relationship
  • Vascular Endothelial Growth Factor A / biosynthesis
  • Water / chemistry

Substances

  • Photosensitizing Agents
  • Porphyrins
  • Quinazolines
  • Vascular Endothelial Growth Factor A
  • Water
  • chlorin