新型尼古丁酸衍生物的合成,具有潜在的抗氧化和抗癌活性
Yara El-Dash1, Nadia A Khalil1, Eman M Ahmed1
1Pharmaceutical Organic Chemistry Department, Faculty of Pharmacy, Cairo University, Cairo, Egypt.
研究人员开发了针对VEGFR-2的新尼古丁酸化合物. 化合物5c表现出强烈的双重细胞毒和抗氧化活性,显示出作为新型癌症治疗剂的前景.
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:
- 血管内皮生长因子受体-2 (VEGFR-2) 是癌症治疗的关键标.
- 开发具有提高选择性的新型细胞毒剂至关重要.
- 尼古丁酸衍生物为药物设计提供了潜在的支架.
研究的目的:
- 设计和合成基于尼古丁酸的新型化合物.
- 评估它们对各种癌症细胞系的细胞毒性疗效.
- 调查它们对VEGFR-2的抑制活性.
主要方法:
- 新型尼古丁酸衍生物的合成.
- 对60个人类癌细胞系进行细胞毒性查.
- 在体外测定VEGFR-2抑制,亡诱导和抗氧化活性.
- 分子对接和ADME分析.
- 密度函数理论 (DFT) 的计算.
主要成果:
- 两个化合物,5b和5c显示出显著的活性.
- 化合物5c在特定细胞系中表现出比多克索鲁比辛和索拉芬尼比较高的细胞毒性.
- 化合物5c显示出强大的VEGFR-2抑制 (IC50 = 0.068μM) 和选择性.
- 化合物5c诱导了亡,并证明了抗氧化能力 (SOD水平).
- 对接研究和ADME分析表明,它具有良好的类似药物的特性.
结论:
- 化合物5c具有双重细胞毒性和抗氧化活性.
- 化合物5c是作为抗癌剂进一步开发的有希望的候选物.
- 新型尼古丁酸支架有效向VEGFR-2.
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