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

  • Bioorg Med Chem Lett. 2026 Aug:137:130632. doi: 10.1016/j.bmcl.2026.130632.
Yuzuha Miyazawa  1 ,  Daisuke Takahashi  1 ,  Kazunobu Toshima  2
Affiliations
  • 1. Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan.
  • 2. Department of Applied Chemistry, Faculty of Science and Technology, Keio University, 3-14-1 Hiyoshi, Kohoku-ku, Yokohama 223-8522, Japan. Electronic address: [email protected].
PMID: 41903766 DOI: 10.1016/j.bmcl.2026.130632
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.

Keywords
Activatable photosensitizer; Anthraquinone; Cancer cell; Glutathione; Photodynamic therapy.
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