Tissue regeneration promotion effects of phenanthroimidazole derivatives through pro-inflammatory pathway activation

Fish Shellfish Immunol. 2018 Sep:80:582-591. doi: 10.1016/j.fsi.2018.06.029. Epub 2018 Jun 18.

Abstract

A chemotherapeutic drug exerts favorable antitumor activity and simultaneously exhibits expectable inhibition on wound healing process. Phenanthroimidazole derivatives possess potent anticancer activity. However, only a few studies focused on the discovery of its potential effects on promoting tissue regeneration. In this study, four novel phenanthroimidazole derivatives were synthesized and characterized, and they exhibited evident inhibition on different tumor cells; compound 3 is the most active one. Moreover, 3 can promote wound healing of zebrafish in a dose-dependent manner. Further study demonstrated that 3 promoted the recruitment of inflammatory cells, formation of angiogenesis, and generation of reactive oxygen species and also influenced the motor behavior of zebrafish. Results indicated that 3 can accelerate the occurrence of pro-inflammation, angiogenesis, oxidative stress, and innervation, which play key roles in the facilitation of wound healing. Therefore, 3 can act as a bifunctional drug in inhibiting tumor and promoting tissue regeneration.

Keywords: Anti-tumor; Phenanthroimidazole derivatives; Wound healing; Zebrafish.

MeSH terms

  • Animal Fins / drug effects*
  • Animal Fins / physiology
  • Animals
  • Animals, Genetically Modified
  • Antineoplastic Agents / pharmacology*
  • Antineoplastic Agents / toxicity
  • Behavior, Animal / drug effects
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Embryo, Nonmammalian / blood supply
  • Embryo, Nonmammalian / drug effects
  • Green Fluorescent Proteins / genetics
  • Humans
  • Imidazoles / pharmacology*
  • Imidazoles / toxicity
  • Inflammation / immunology
  • Larva / drug effects
  • Larva / immunology
  • Locomotion / drug effects
  • Neovascularization, Physiologic / drug effects
  • Reactive Oxygen Species / immunology
  • Regeneration / drug effects*
  • Wound Healing / drug effects
  • Zebrafish / genetics

Substances

  • Antineoplastic Agents
  • Imidazoles
  • Reactive Oxygen Species
  • enhanced green fluorescent protein
  • Green Fluorescent Proteins