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March 29, 2026Bioorganic & Medicinal Chemistry Letters0 citationsOpen Access

A glutathione-activated anthraquinone-based photosensitizer for selective photodynamic therapy of cancer cells overexpressing glutathione

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YMYuri MiyazawaDTDaisuke TakahashiKTKazunobu Toshima

Key Points

  • The study aims to develop a glutathione-activated photosensitizer that selectively targets cancer cells with high GSH levels.
  • Designed and synthesized an anthraquinone-based photosensitizer that activates with glutathione.
  • Evaluated the cytotoxic effects of the photosensitizer under visible light irradiation.
  • Compared photoactivity in the presence and absence of glutathione.
  • The photosensitizer exhibited minimal activity without GSH.
  • In the presence of GSH, it generated a highly active species with selective cytotoxic effects on cancer cells.
  • The developed system showed potential for targeted photodynamic therapy.

Abstract

An anthraquinone derivative 2 was found to induce protein degradation under neutral conditions and without additives upon visible light irradiation. Based on this finding, a glutathione (GSH)-activatable photosensitizer 3 was designed and synthesized. 3 showed minimal photoactivity in the absence of GSH, but upon reaction with GSH, it generated a highly active species that caused selective photo-cytotoxicity toward cancer cells with elevated intracellular GSH levels. These results demonstrate the potential of anthraquinone-based systems as tunable and tumor-selective photosensitizers for photodynamic therapy. • A simple anthraquinone derivative 2 was found to degrade proteins upon irradiation with visible light. • A novel glutathione (GSH)-activatable photosensitizer 3 was designed and synthesized based on 2 . • 3 showed negligible photosensitizing ability in the absence of GSH. • 3 exhibited photo-cytotoxicity against only cancer cells expressing high levels of GSH when irradiated with visible light.

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Cite This Study

Miyazawa et al. (2026) studied this question.

synapsesocial.com/papers/69c8c15ade0f0f753b39bd68https://doi.org/10.1016/j.bmcl.2026.130632
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