2. Academic Validation
  3. Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity

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

  • ACS Med Chem Lett. 2020 Nov 23;11(12):2491-2496. doi: 10.1021/acsmedchemlett.0c00484.
Toghrul Almammadov 1,  Gizem Atakan 2,  Ozen Leylek 3,  Gulnihal Ozcan 4,  Gorkem Gunbas 2,  Safacan Kolemen 1 5 6 7
Affiliations

Affiliations

  • 1 Department of Chemistry, Koc University, Sariyer, 34450 Istanbul Turkey.
  • 2 Department of Chemistry, Middle East Technical University (METU), 06800 Ankara, Turkey.
  • 3 Graduate School of Health Sciences, Koc University, 34450 Istanbul, Turkey.
  • 4 Department of Medical Pharmacology, School of Medicine, Koc University, 34450 Istanbul, Turkey.
  • 5 Surface Science and Technology Center (KUYTAM), Koc University, Sariyer, 34450 Istanbul, Turkey.
  • 6 Boron and Advanced Materials Application and Research Center, Koc University, Sariyer, 34450 Istanbul, Turkey.
  • 7 TUPRAS Energy Center (KUTEM), Koc University, Sariyer, 34450 Istanbul, Turkey.
PMID: 33335672 DOI: 10.1021/acsmedchemlett.0c00484
Abstract

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 1O2 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-SY5Y 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.

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