含有1,2,3-三醇部分的杜洛特格拉维尔衍生物的合成和抗瘤活性
Xixi Hou1, Longfei Mao2,3, Yajie Guo4
1Department of Pharmacy, The First Affiliated Hospital, and College of Clinical Medicine of Henan University of Science and Technology, Luoyang, 471003, China.
BMC chemistry
|May 7, 2024
概括
新型多洛特格拉维尔衍生物被合成并测试了抗癌性质. 两个化合物,9e和9p通过诱导细胞灭绝和改变细胞周期,对肺癌细胞表现出强大的抗瘤活性,其中9e对正常细胞具有低毒性.
科学领域:
- 药用化学 医学化学
- 药理学 药理学是指药理学的学科.
- 癌症生物学 癌症生物学
背景情况:
- 药物修饰对于开发更安全,更适用的治疗方法至关重要.
- 氧-异循环是新药发现的重要支架.
- 杜鲁特格拉维尔是一种艾滋病毒药物,具有潜在的抗癌特性.
研究的目的:
- 合成新型的杜洛特格拉维尔衍生物,其中包含1,2,3-三醇部分.
- 评估这些新化合物对肺癌细胞系的抗瘤疗效.
- 调查它们的抗癌作用背后的机制.
主要方法:
- 使用点击化学合成多洛特格拉维尔衍生物.
- 在多个肺癌细胞系中的体外抗瘤活性评估 (PC-9,H460,A549).
- 对亡诱导,细胞增殖抑制,细胞周期变化,活性氧物种 (ROS) 水平和LC3蛋白表达的分析.
主要成果:
- 化合物9e和9p表现出显著的抗瘤活性,IC50值低至3.17μM对PC-9细胞.
- 这两种化合物都有效地抑制了PC-9和H460细胞的增殖和诱导的亡.
- 化合物9e和9p调节了ROS水平和增加了LC3蛋白表达,表明氧化应激和自途径的参与.
结论:
- 新型杜洛泰格拉维尔衍生品表现出强大的抗肺癌活性.
- 化合物9e和9p代表了对进一步抗癌药物开发有前途的化合物.
- 抗癌效应通过诱导亡,细胞循环停止和ROS和自的调节来调节.
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