Synthesis, photophysical properties and biological evaluation of β-alkylaminoporphyrin for photodynamic therapy

Bioorg Med Chem. 2016 Nov 15;24(22):6040-6047. doi: 10.1016/j.bmc.2016.09.060. Epub 2016 Sep 26.

Abstract

A series of β-alkylaminoporphyrins conjugated with different amines at β position (D1-D3) or with electron-donating and electron-withdrawing substituents at phenyl position (D4-D6) were synthesized. Their photophysical and photochemical properties, intracellular localization, photocytotoxicities in vitro and vivo were also investigated. All target compounds exhibited no cytotoxicities in the dark and excellent photocytotoxicities against HeLa cells. Among them, D6 showed the highest phototoxicity and the lowest dark toxicity, which was more phototoxic than Hematoporphyrin monomethyl ether (HMME). In addition, D6 exhibited best photodynamic antitumor efficacy on BALB/c nude mice bearing HeLa tumor. Therefore, D6 is a powerful and promising antitumor photosensitizer for photodynamic therapy.

Keywords: Antitumor; Photodynamic therapy; Photosensitizer; Tetraphenylporphyrin.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Female
  • HeLa Cells
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Structure
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / pathology
  • Photochemical Processes
  • Photochemotherapy*
  • Porphyrins / chemical synthesis
  • Porphyrins / chemistry
  • Porphyrins / pharmacology*
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Porphyrins