基纳林硫胺衍生物向MicroRNA-34a/MDM4/p53的核突轴,具有辐射敏感活性
Aiten M Soliman1, Ahmad S Kodous2, Diana A Al-Sherif3
1Drug Radiation Research Department, National Center for Radiation Research & Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo 11787, Egypt.
Future medicinal chemistry
|April 25, 2024
概括
新的奇纳二硫胺混合物,特别是4d化合物,通过调节miR-34a/MDM4/p53亡途径,表现出强大的抗癌活性. 它的有效性由马辐射增强,表明治疗潜力.
科学领域:
- 药用化学 医学化学
- 分子生物学分子生物学
- 癌症研究 癌症研究
背景情况:
- 基纳二二硫胺混合物正在探索抗癌性质.
- 在调节亡和瘤抑制方面,miR-34a/MDM4/p53通路至关重要.
研究的目的:
- 合成新型纳素二硫胺混合物 (4a-n).
- 评估它们对各种癌症细胞系的细胞毒性.
- 研究它们对miR-34a/MDM4/p53亡途径的影响.
主要方法:
- 合成金纳林二硫胺混合物.
- 使用MTT测定对肝,乳腺,肺癌和结肠癌细胞系进行细胞毒性评估.
- 对基因表达的分析 (miR-34a,p53,miR-21,VEGF,STAT3,MDM4).
- 分子对接研究针对VEGFR2和MDM4.
主要成果:
- 化合物4d对HepG2和MCF-7细胞表现出显著的细胞毒性.
- 化合物4d上调了miR-34a和p53基因表达,表明了亡诱导.
- 化合物4d降低了miR-21,VEGF,STAT3和MDM4基因表达的调节.
- 4d的抗癌和亡活性被8 Gy马辐射增强.
- 对接分析显示,4d对VEGFR2和MDM4.4具有良好的结合亲和力.
结论:
- 化合物4d表现出强大的抗癌和亡活性.
- 该机制涉及对miR-34a/MDM4/p53通路的调制.
- 与马辐射的联合疗法可能会增强化合物4d的治疗疗效.
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