试卤灵进入光动力治疗领域：一种用于选择性细胞毒性的单胺氧化酶可激活剂。
Resorufin Enters the Photodynamic Therapy Arena: A Monoamine Oxidase Activatable Agent for Selective Cytotoxicity.
作者信息
Almammadov Toghrul, Atakan Gizem, Leylek Ozen, Ozcan Gulnihal, Gunbas Gorkem, Kolemen Safacan
机构信息
Department of Chemistry, Koc University, Sariyer, 34450 Istanbul Turkey.
Department of Chemistry, Middle East Technical University (METU), 06800 Ankara, Turkey.
出版信息
ACS Med Chem Lett. 2020 Nov 23;11(12):2491-2496. doi: 10.1021/acsmedchemlett.0c00484. eCollection 2020 Dec 10.
A red-absorbing, water-soluble, and iodinated resorufin derivative () that can be selectively activated with a monoamine oxidase (MAO) enzyme was synthesized, and its potential as a photodynamic therapy (PDT) agent was evaluated. showed high O generation yields in aqueous solutions upon addition of MAO isoforms, and it was further tested in cell culture studies. 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, displayed differential cytotoxicity between cancer and normal cells, without any considerable dark toxicity. To the best of our knowledge, 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.
合成了一种可被单胺氧化酶（MAO）选择性激活的红色吸收、水溶性且碘化的试卤灵衍生物（），并评估了其作为光动力疗法（PDT）剂的潜力。添加MAO同工型后，在水溶液中显示出高的O生成产率，并在细胞培养研究中进一步进行了测试。在内源性MAO酶触发后，在癌细胞中诱导光细胞毒性，在具有高MAO - A表达的SH - SY5Y神经母细胞瘤细胞中效率更高。此外，在癌细胞和正常细胞之间表现出差异细胞毒性，没有任何明显的暗毒性。据我们所知，这标志着基于试卤灵的光敏剂（PS）的首个实例以及首个由MAO酶激活的抗癌药物。值得注意的是，由于通用的试卤灵化学，仅通过三个步骤就获得了目标PDT剂。
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