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

Authors :: Almammadov T
Atakan G
Leylek O
Ozcan G
Gunbas G
Kolemen S
Source :: ACS medicinal chemistry letters [ACS Med Chem Lett] 2020 Nov 23; Vol. 11 (12), pp. 2491-2496. Date of Electronic Publication: 2020 Nov 23 (Print Publication: 2020).
Publication Year :: 2020
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 <superscript>1</superscript> O <subscript>2</subscript> 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.<br />Competing Interests: The authors declare no competing financial interest.<br /> (© 2020 American Chemical Society.)

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