Synthesis and biological evaluation of 173-dicarboxylethyl-pyropheophorbide-a amide derivatives for photodynamic therapy

Bioorg Med Chem Lett. 2018 Sep 1;28(16):2784-2788. doi: 10.1016/j.bmcl.2017.12.034. Epub 2017 Dec 19.

Abstract

Three novel 173-dicarboxylethyl-pyropheophorbide-a amide derivatives as photosensitizers for photodynamic therapy (PDT) were synthesized from pyropheophorbide-a (Ppa). Their photophysical and photochemical properties, intracellular localization, photocytotoxicity in vitro and in vivo were investigated. All target compounds exhibited low cytotoxicity in the dark and remarkable photocytotoxicity against human esophageal cancer cells. Among them, 1a showed highest singlet oxygen quantum yield. Upon light activation, 1a exhibited significant photocytotoxicity. After PDT treatment, the growth of Eca-109 tumor in nude mice was significantly inhibited. Therefore, 1a is a powerful and promising antitumor photosensitizer for PDT.

Keywords: Chlorin; Chlorophyll; Photodynamic therapy; Photosensitizer; Tumor.

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
  • Cell Survival / drug effects
  • Chlorophyll / analogs & derivatives
  • Chlorophyll / chemical synthesis
  • Chlorophyll / chemistry
  • Chlorophyll / pharmacology*
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Humans
  • Mice
  • Mice, Inbred BALB C
  • Mice, Nude
  • Molecular Conformation
  • Neoplasms, Experimental / drug therapy
  • Neoplasms, Experimental / metabolism
  • Neoplasms, Experimental / pathology
  • Photochemotherapy*
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology*
  • Singlet Oxygen / chemistry
  • Singlet Oxygen / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Photosensitizing Agents
  • Chlorophyll
  • Singlet Oxygen