呋咱及二氢卟吩e6缀合物的合成及光动力抗肿瘤活性评价
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TQ463

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国家自然科学基金(21506024;辽宁省自然科学基金(2019-MS-060);中央高校基本科研业务费(DUT20LK08)


Synthesis of furoxan and chlorin e6 conjugate and evaluation of photodynamic antitumor activity
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National Natural Science Foundation of China; Natural Science Foundation of Liaoning Province; Fundamental Research Funds for Central Universities

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    摘要:

    光动力治疗(PDT)是一种无创治疗肿瘤的方法,其特点是利用特定波长的光,激发富集于肿瘤细胞中的光敏剂,产生具有细胞毒性的活性氧(ROS),诱导细胞损伤及死亡,但肿瘤组织附近氧气浓度低,限制了光敏剂产生活性氧的水平,影响了PDT的治疗效果。本文以苯丙烯醇为原料,合成了4-苯基-3-羟甲基-氧化呋咱,与二氢卟吩e6经酯化反应,得到含有呋咱的二氢卟吩e6缀生物。活性评价结果表明,呋咱基团的引入,可以明显提高细胞内NO水平,增强细胞内ROS数量,协同提高光动力抑制肿瘤细胞增殖活性约20倍。本研究结果表明,在光敏剂结构中,引入呋咱类NO供体结构,能显著提高光敏剂的抑制肿瘤细胞增殖的活性,为新型、高效的光敏抗肿瘤治疗剂的合成提供了新的思路。

    Abstract:

    Photodynamic therapy (PDT) is a non-invasive method of treating tumors.It is characterized by using light of a specific wavelength to excite the photosensitizer enriched in tumor cells to produce cytotoxic reactive oxygen species (ROS), and induce cell damage and death. However, the low oxygen concentration near the tumor tissue limits the level of active oxygen produced by the photosensitizer and affects the therapeutic effect of PDT. Using phenylpropenol as a raw material, 4-phenyl-3-hydroxymethyl-furoxan was synthesized, and it was esterified with chlorin e6 to obtain a chlorin e6 conjugate containing furazan. The results of the activity evaluation showed that the introduction of furazan group can significantly increase the level of intracellular NO, increase the number of intracellular ROS, and synergistically increase the photodynamic inhibitory activity of tumor cell proliferation by about 20 times. The results of this study indicate that the introduction of furoxan-like NO donor structure in the photosensitizer structure can significantly improve the photosensitizer’s activity in inhibiting tumor cell proliferation, providing a new idea for the synthesis of new and efficient photosensitizing anti-tumor therapeutic agents .

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于昊泽,申万洁,王世盛,周凯悦,郭修晗.呋咱及二氢卟吩e6缀合物的合成及光动力抗肿瘤活性评价[J].精细化工,2021,38(9):

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  • 收稿日期:2021-03-22
  • 最后修改日期:2021-04-28
  • 录用日期:2021-04-28
  • 在线发布日期: 2021-08-05
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