具有高选择性和低毒性的新CDDO甲酸乙衍生物
Na Li1,2, Junjie Wang1, Lulu Zhang1
1State Key Laboratory of Natural Medicines, Department of Natural Medicinal Chemistry, School of Traditional Chinese Pharmacy, China Pharmaceutical University, 639 Longmian Avenue, Nanjing 211198, China.
一种新型的烯酸衍生物,化合物4,通过利用高反应性氧物种 (ROS) 水平,显示出对癌细胞的增强选择性. 与CDDO-Me.Me相比,这种修改策略可以提高抗癌疗效和瘤抑制.
科学领域:
- 药用化学 医学化学
- 有机化学 有机化学
- 癌症生物学 癌症生物学
背景情况:
- 烯酸衍生物,如CDDO-Me,通常缺乏瘤选择性.
- 癌细胞表现出高水平的活性氧物种 (ROS).
研究的目的:
- 设计和合成具有改善癌细胞选择性的新型CDDO甲酸乙烯衍生物.
- 为了评估化合物4,一个有前途的CDDO衍生物的疗效和安全性.
主要方法:
- 合成了 17 种新的 CDDO 甲基酸乙烯衍生物.
- 使用BGC-823癌细胞进行体外抗增殖试验.
- 在ICR小鼠中的体内药理动力学和瘤抑制研究.
主要成果:
- 在测试的衍生物中,化合物4对癌细胞具有最高的选择性.
- ROS转化化合物4到4H,增强共价结合和抗扩散 (IC50:0.37μM对2.11μM).
- 化合物4通过增加ROS水平,在BGC-823细胞中诱导了亡,其LD50 (91.2 mg/kg) 和瘤抑制率 (86.2%) 比CDDO-Me.Me.更高.
结论:
- 化合物4代表了CDDO的有效修饰,显著增加了癌细胞选择性.
- 由ROS触发的4H转化为4H是其增强抗癌活性的一个关键机制.
- 这一战略为开发更有针对性的癌症治疗方法提供了一个有希望的方法.
更多相关视频
13:35A Convenient Method for Extraction and Analysis with High-Pressure Liquid Chromatography of Catecholamine Neurotransmitters and Their Metabolites
Published on: March 1, 2018
08:46Regioselective O-Glycosylation of Nucleosides via the Temporary 2',3'-Diol Protection by a Boronic Ester for the Synthesis of Disaccharide Nucleosides
Published on: July 26, 2018
相关概念视频
Diels–Alder Reaction Forming Bridged Bicyclic Products: Stereochemistry
Alkylation of β-Diester Enolates: Malonic Ester Synthesis
meta-Directing Deactivators: –NO2, –CN, –CHO, –⁠CO2R, –COR, –CO2H
ortho–para-Directing Activators: –CH3, –OH, –⁠NH2, –OCH3
Regioselectivity and Stereochemistry of Hydroboration
Hydroboration proceeds in a concerted fashion with the attack of borane on the π bond, giving a cyclic four-centered transition state. The –BH2 group is bonded to the less substituted carbon and –H to the more substituted carbon. The concerted nature requires the simultaneous addition of –H and –BH2 across the same face of the alkene giving syn...
Diels–Alder Reaction: Characteristics of Dienophiles
Characteristics of Dienophiles
Generally, the best dienophiles are alkenes containing electron-withdrawing substituents such as carbonyl, nitrile, and nitro groups. The feasibility of a Diels–Alder reaction depends...
