Synthesis and photo-induced anticancer activity of new 2-phenylethenyl-1H-benzo[e]indole dyes

Eur J Med Chem. 2024 Nov 5:277:116777. doi: 10.1016/j.ejmech.2024.116777. Epub 2024 Aug 13.

Abstract

Herein, a series of new 1,1,2-trimethyl-1H-benzo[e]indole dyes was prepared via Knoevenagel condensation reaction between 1,1,2-trimethyl-1H-benzo[e]indole and benzaldehydes, and characterized using various spectroscopic methods. The obtained compounds showed cytotoxic properties in G361 melanoma cell line upon irradiation with 414 nm blue light at submicromolar doses. The mechanism of action of the most potent compound 15 was further investigated. The treatment induced substantial generation of reactive oxygen species, leading to DNA damage followed by cell death depending on the concentration of the photosensitizer compound and the irradiation intensity.

Keywords: DNA damage; Knoevenagel condensation; benzo[e]indole; photo-induced activity; reactive oxygen species.

MeSH terms

  • Antineoplastic Agents* / chemical synthesis
  • Antineoplastic Agents* / chemistry
  • Antineoplastic Agents* / pharmacology
  • Cell Line, Tumor
  • Cell Proliferation / drug effects
  • Coloring Agents / chemical synthesis
  • Coloring Agents / chemistry
  • Coloring Agents / pharmacology
  • DNA Damage / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor*
  • Humans
  • Indoles* / chemical synthesis
  • Indoles* / chemistry
  • Indoles* / pharmacology
  • Light
  • Molecular Structure
  • Photosensitizing Agents / chemical synthesis
  • Photosensitizing Agents / chemistry
  • Photosensitizing Agents / pharmacology
  • Reactive Oxygen Species / metabolism
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indoles
  • Reactive Oxygen Species
  • Photosensitizing Agents
  • Coloring Agents