通过调整二氧化联体的电子结构来增加Ru (II) 聚烯基复合物的细胞毒性
Anna Notaro, Marta Jakubaszek1, Nils Rotthowe2
1Institut Curie, PSL University, CNRS, UMR 144, F-75005 Paris, France.
Journal of the American Chemical Society
|February 29, 2020
概括
这项研究探讨了复合物作为抗癌剂,发现电子捐赠组 (1-4复合物) 的细胞毒性高于电子取消组 (5-6复合物) 的细胞毒性. 由于其高效率和多个细胞点,复合1是一种有前途的化疗候选药物.
科学领域:
- 协调化学
- 药用无机化学
- 化学生物学
背景情况:
- 复合物显示出作为抗癌药物候选物的显著潜力.
- 结构与活性之间的关系对于优化药物的有效性和向至关重要.
- 在Ru-sq复合体中的半联体提供了衍生化的平台.
研究的目的:
- 对新型的酸盐复合物进行结构-活性关系 (SAR) 研究.
- 研究电子捐赠和电子吸收组对复杂性质和抗癌活性的影响.
- 确定化学疗法研究的有前途的候选人.
主要方法:
- 合成和表征六个复合物 (1-6) 具有不同的甲基酸配体.
- 包括电荷,颜色和配体氧化状态在内的物理化学性质的研究.
- 对癌细胞系和细胞吸收机制的体外细胞毒性评估.
主要成果:
- 复合物1-4 (具有电子捐赠组) 具有正电荷,深红色,并且比中性,蓝色/紫色复合物5-6 (具有电子吸收组) 具有显著更高的细胞毒性 (IC50=0. 07- 0. 7μM).
- 综合体1通过被动运输和在各种细胞区 (细胞核,溶酶体,线粒体,细胞质) 中的中度积累证明了有效的细胞吸收.
- 复合物1与DNA直接相互作用,并导致线粒体功能受损,表明多种作用模式.
结论:
- 甲基酸连体的性质 (EDG与EWG) 极大地影响了复合物的物理化学和生物特性.
- 由于其强大的细胞毒性,多目标作用和有利的细胞吸收,复合物1是一种非常有前途的抗癌候选物.
- 预先的生物分布研究表明,复合物1适合在化疗研究中进行进一步的体内评估.
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