在基于Ir(III) -COUPY结合物的光动力疗法抗癌剂中探索结构-活性关系
Anna Rovira1, Enrique Ortega-Forte2, Cormac Hally3
1Departament de Química Inorgànica i Orgànica, Secció de Química Orgànica, Universitat de Barcelona (UB), and Institut de Biomedicina de la Universitat de Barcelona (IBUB), Martí i Franquès 1-11, E-08028 Barcelona, Spain.
Journal of medicinal chemistry
|June 2, 2023
概括
研究人员开发了新型光动力学治疗 (PDT) 剂,使用 ((III) -COUPY合物来对抗耐药性癌症. 这些药物即使在低氧条件下也表现出高光毒性和有效性,为耐思细胞提供了有前途的非侵入性治疗方法.
科学领域:
- 化学 化学 化学
- 生物医学工程 生物医学工程
- 在瘤学瘤学.
背景情况:
- 光动力疗法 (PDT) 是对耐药癌症的一种有前途的非侵入性治疗方法.
- 开发有效的,无毒的光敏化剂,特别是对于低氧条件的发展至关重要.
研究的目的:
- 设计和合成基于 ((III) - COUPY合物的新型PDT剂.
- 探索影响光物理性质和抗癌功效的结构-活性关系.
- 评估这些药物在正常和缺氧条件下对抗抗的癌细胞的疗效.
主要方法:
- ((III) -COUPY结合物的合成,在氨酸支架上具有结构变化.
- 光物理性质的表征 (例如,光毒性,ROS生成).
- 在A2780cis癌细胞中细胞吸收和光疗疗效的体外评估.
主要成果:
- 库马林支架的结构性修改显著影响了光物理性质和细胞吸收.
- 所有合成的Ir(III) -COUPY合物在通过活性氧物种 (ROS) 生成的绿光照射下显示出高光毒性.
- 两种联体在抗西斯普拉丁的A2780cis细胞中表现出显著的光疗效应,即使在低氧条件下.
结论:
- 合物是有效的PDT药物,具有强大的抗癌活性.
- 这些药物可以克服癌细胞中获得的西斯普拉丁耐药性.
- 与过渡金属复合物的远红/NIR发射COUPY染料的结合为先进的光疗提供了一个可行的策略.
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