阿森-1 是一种双药抗癌剂
Đenana Miodragović1,2, Antonello Merlino3, Elden P Swindell1
1Chemistry of Life Processes Institute , Northwestern University , 2145 Sheridan Road , Evanston , Illinois 60208 , United States.
Journal of the American Chemical Society
|April 4, 2019
概括
与其原始药物相比,Arsenoplatin-1是一种新型抗癌药物,对各种癌症细胞系具有更高的活性. 这种化合物有效地将和送到癌细胞中,
科学领域:
- 医学化学
- 癌症生物学
- 药物发现
背景情况:
- 甲与三氧化物结合,形成新的抗癌药物.
- 三氧化在血液癌症中有效,但由于快速清除,在固体瘤中受到限制.
- 甲-1 (AP-1) 是该类中的第一个化合物,具有增强的活性.
研究的目的:
- 评估与NCI-60人类瘤细胞系对抗的阿森-1 (AP-1) 的抗癌活性.
- 研究AP-1与蛋白质和DNA的生物相互作用.
- 了解和物种的作用和传递机制.
主要方法:
- 对NCI-60癌细胞系进行AP-1活性查.
- 对AP-1与模型蛋白结合的结构研究.
- 分析AP-1与DNA的相互作用,包括时间上的Pt:As比率.
主要成果:
- 与西斯和三氧化相比,AP-1 在大多数测试细胞系中表现出优异的抗癌活性.
- 结构研究表明与蛋白质中的His残留物结合,从而保留Pt-As键.
- AP-1 进入细胞并最初与完整的 Pt-As 键结合DNA,后来释放了部分.
结论:
- 阿森1具有显著的抗癌能力,在各种癌症类型中表现优于其原始药物.
- 该化合物最初保留 Pt-As 键,然后释放的能力表明它具有双交付机制.
- 通过输送和物种, AP-1 具有治疗血液和固体瘤的潜力.
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