Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity

Almammadov T., ATAKAN G. , Leylek O., Ozcan G., Gunbas G. , Kolemen S.

ACS MEDICINAL CHEMISTRY LETTERS, vol.11, no.12, pp.2491-2496, 2020 (Journal Indexed in SCI) identifier identifier identifier

  • Publication Type: Article / Article
  • Volume: 11 Issue: 12
  • Publication Date: 2020
  • Doi Number: 10.1021/acsmedchemlett.0c00484
  • Page Numbers: pp.2491-2496
  • Keywords: Photodynamic therapy, activatable photosensitizers, resorufin, cancer cell selectivity, monoamine oxidase, SINGLET OXYGEN, CELL-DEATH, PHOTOSENSITIZER, GENERATION, PROBES


A red-absorbing, water-soluble, and iodinated resorufin derivative (R1) that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. R1 showed high O-1(2) generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. R1 induced photocytotoxicity after being triggered by endogenous MAO enzyme in cancer cells with a much higher efficiency in SH-SYSY neuroblastoma cells with high MAO-A expression. Additionally, R1 displayed differential cytotoxicity between cancer and normal cells, without any considerable dark toxicity. To the best of our knowledge, R1 marks the first example of a resorufin-based photosensitizer (PS) as well as the first anticancer drug that is activated by a MAO enzyme. Remarkably, the target PDT agent was obtained only in three steps as a result of versatile resorufin chemistry.