基于Pt(IV) 复合物的有前途的抗癌原药与轴位置的双有机联体
Francisco Navas1, Ana Chocarro-Calvo2, Patricia Iglesias-Hernández3
1Group of Chemical and Environmental Engineering, Rey Juan Carlos University. C/Tulipán s/n, Móstoles, Madrid28933, Spain.
Journal of medicinal chemistry
|April 9, 2024
概括
开发了两种新的 (IV) 抗癌前期药物. 与西斯普拉丁相比,Pt(IV) -biSi-2对结直肠癌细胞和瘤的疗效优越,副作用减少.
科学领域:
- 药用化学 医学化学
- 癌症生物学 癌症生物学
- 药物开发 药物开发
背景情况:
- 基药物如思是癌症化疗的主要支柱.
- 开发新的 (IV) 前药物为提高疗效和降低毒性提供了潜在的潜力.
- 有机联体为设计先进 (IV) 复合体提供了一个有前途的途径.
研究的目的:
- 合成和表征两种新白金(IV) 预制药与 bis-organosilane 连接体.
- 评估这些新型化合物的体外和体内抗癌活性.
- 阐明作用机制,并将疗效与西斯普拉丁进行比较.
主要方法:
- 合成和表征两个 (IV) 复合物,Pt (IV) -biSi-1和Pt (IV) -biSi-2.
- 在体外细胞毒性测定对结肠癌细胞系 (HCT 116,HT-29) 和正常肠道细胞 (HIEC6).
- 在直肠癌的临床前小鼠模型中的体内疗效研究和DNA损伤诱导的机制研究.
主要成果:
- 与西斯普拉丁和Pt(IV) -biSi-1相比,Pt(IV) -biSi-2在实验室中对结肠癌细胞表现出增强的细胞毒性.
- Pt(IV) -biSi-2对癌细胞有较高的毒性,对正常肠道细胞有较低的毒性.
- 在体内,Pt(IV) -biSi-2 降低了瘤生长,在较低剂量和较少副作用下,比西斯普拉丁更有效.
- 从机制上讲,Pt(IV) -biSi-2诱导了永久的DNA损伤,与西斯普拉丁的短暂作用不同,这是由于更快的减少到活跃的Pt(II) 物种.
结论:
- 成功开发了新的 (IV) 预药物,其中含有 bis-organosilane 配体.
- Pt(IV) -biSi-2表现出优异的抗癌活性和对结直肠癌的特异性,表现优于思丁.
- 这项研究为设计下一代基于的抗癌疗法提供了一个有前途的战略,该疗法具有更好的安全性和有效性.
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