作为潜在的癌症治疗药物,Calix[4]arene-pyrazole结合剂可以作为潜在的癌症治疗药物
Anton A Muravev1, Alexandra D Voloshina2, Anastasia S Sapunova2
1Infochemistry Scientific Center, ITMO University, Lomonosov Str. 9, 191002 Saint Petersburg, Russia; Arbuzov Institute of Organic and Physical Chemistry, FRC Kazan Scientific Center of RAS, Arbuzov Str. 8, 420088 Kazan, Russia.
Bioorganic chemistry
|July 22, 2023
概括
新的calixarene pyrazoles显示选择性杀死癌细胞,具有低毒性. 这些化合物诱导M-HeLa细胞的亡和DNA损伤,为化疗提供了一个有前途的途径.
科学领域:
- 药用化学 医学化学
- 在瘤学瘤学.
- 分子生物学分子生物学
背景情况:
- 化疗在瘤选择性方面面临挑战.
- 开发具有向细胞毒性的新型抗癌药物至关重要.
研究的目的:
- 合成和表征新型的卡利克萨林皮拉.
- 评估它们对各种癌症细胞系的选择性细胞毒性.
- 研究作用机制和毒性概况.
主要方法:
- 素衍生物的合成和表征.
- 在体外细胞毒性测定使用M-HeLa,MCF7,A-549,PC3,Chang肝和Wi38细胞.
- 诱导亡的分析 (caspase-9激活,细胞循环停止).
- 评估DNA损伤标记物和DNA相互作用研究.
- 在小鼠体内有毒性研究.
主要成果:
- 对于含有 tert-butylcalix[4]arene pyrazoles (化合物 7b 和 7c) 的 M-HeLa 细胞观察到的特定细胞毒性.
- 化合物7b和7c具有较低的致变性,血液毒性和体内毒性.
- 通过caspase-9激活和G0/G1细胞循环停止诱导线粒体亡途径.
- 过度表达DNA损伤标记物和证据显示卡利沙林与DNA相互作用.
结论:
- 卡利克萨伦pyrazoles表现出有希望的瘤选择性.
- 化合物7b和7c代表了针对癌症治疗的潜在化合物.
- 该机制涉及DNA向和诱导亡.
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