Synthesis of 2-morpholinetetraphenylporphyrins and their photodynamic activities

Bioorg Chem. 2017 Apr:71:299-304. doi: 10.1016/j.bioorg.2017.02.015. Epub 2017 Feb 27.

Abstract

A series of 2-morpholinetetraphenylporphyrins functionalized with various substituents (Cl, Me, MeO group) at 4-phenyl position were prepared via nucleophilic substitution of 2-nitroporphyrin copper derivatives with morpholine by refluxing under a nitrogen atmosphere and then demetalization. Their basic photophysical properties, intracellular localization, cytotoxicities in vitro and in vivo were also investigated. All synthesized photosensitizers exhibited longer maxima absorption wavelengths than Hematoporphyrin monomethyl ether (HMME). They showed low dark cytotoxicity compared with that of HMME and were more phototoxic than HMME against Eca-109 cells in vitro. M3 also exhibited better photodynamic antitumor efficacy on BALB/c nude mice at a lower concentration. Therefore, M3 is a promising antitumor photosensitizer in photodynamic therapy application.

Keywords: Antitumor; Photodynamic therapy; Photosensitizer; Porphyrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Female
  • Hematoporphyrins / pharmacology
  • Humans
  • Mice, Inbred BALB C
  • Mice, Nude
  • Morpholines / chemical synthesis
  • Morpholines / chemistry*
  • Morpholines / pharmacology
  • Morpholines / therapeutic use*
  • Neoplasms / drug therapy*
  • Photochemotherapy
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry*
  • Photosensitizing Agents / pharmacology
  • Photosensitizing Agents / therapeutic use*
  • Porphyrins / chemical synthesis
  • Porphyrins / chemistry*
  • Porphyrins / pharmacology
  • Porphyrins / therapeutic use*

Substances

  • 5,10,15,20-tetraphenylporphyrin
  • Hematoporphyrins
  • Morpholines
  • Photosensitizing Agents
  • Porphyrins
  • hematoporphyrin monomethyl ether