基于昆的 thiazolyl-hydrazones 通过抑制自细胞来向癌细胞
Vladimir Ćurčić1, Mateusz Olszewski2, Natalia Maciejewska2
1Faculty of Chemistry, University of Belgrade, Belgrade, Serbia.
Archiv der Pharmazie
|November 22, 2023
概括
合成了新型的 thiazolyl-hydrazone 化合物,并对抗癌活性进行了测试. 化合物3c通过阻止癌症细胞周期进展和诱导DNA损伤,导致细胞死亡,显示出显著的潜力.
科学领域:
- 药用化学 医学化学
- 有机合成 有机合成
- 药理学 药理学 是一个学科.
背景情况:
- 异环化合物,特别是 thiazole 和 quinoline 环,在药物化学中至关重要.
- 这些结构在几种FDA批准的抗癌药物中发现,突出显示了它们的意义.
- 像这样的特权结构为开发新治疗剂提供了坚实的基础.
研究的目的:
- 合成新型的 thiazolyl-hydrazone 化合物,其中包含林部分.
- 评估这些化合物的 in silico ADMET 概况和 in vitro 抗癌活性.
- 为了确定癌症治疗的有前途的候选药物.
主要方法:
- 基于8-oline,2-oline和8-hydroxy-2-quinolyl支架的新型 thiazolyl-hydrazones 的合成.
- 吸收,分布,新陈代谢,分泌和毒性 (ADMET) 属性的体评估.
- 在人体癌细胞系和正常细胞系组对抗癌症活性的体外评估 (HEK-293).
主要成果:
- 化合物3c, [2-(2-(金-8-ol-2-ylmethylene (hydrazinyl) ]-4-(4-methoxyphenyl) -1,3-thiazole,成为最强大的抗癌剂.
- 发现化合物3c在S阶段阻止了人类结肠癌细胞 (HCT-116) 的细胞周期.
- 3c诱导DNA双链断裂并积聚在溶酶体中,通过抑制肝细胞癌 (Hep-G2) 和HCT-116细胞的自细胞死亡.
结论:
- 合成的 thiazolyl-hydrazone 衍生物,特别是 3c 化合物,显示出显著的抗癌潜力.
- 化合物3c表现出双重作用机制,包括细胞循环停止,DNA损伤和自抑制.
- 这些发现支持3c的发展,作为针对特定癌症类型的新疗法策略.
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