为抗癌应用设计,合成和生物评估erlotinib-1,2,3-triazole衍生物
Qiyan Yao1, Kexin Qu1, Lan Wang1
1College of Basic Medicine and Forensic Medicine, Henan University of Science and Technology China sanqiangli2001@163.com.
新的erlotinib衍生物在肝细胞癌 (HCC) 治疗中显示出有前途. 化合物3d在体外和体内表现出显著的抗瘤活性,毒性最小,这表明它有可能成为HCC的新治疗剂.
科学领域:
- 药用化学 医学化学
- 癌症生物学 癌症生物学
- 药理学 药理学是指药理学的学科.
背景情况:
- 肝细胞癌 (HCC) 治疗面临着像erlotinib这样的当前疗法所面临的挑战,需要新的方法.
- 现有单疗法和组合疗法的有限疗效凸显了对新型HCC药物的未满足的临床需求.
研究的目的:
- 为潜在的HCC治疗设计和合成具有1,2,3-triazole部分的新型erlotinib衍生物.
- 评估这些新型化合物的体外和体外抗瘤疗效和安全性.
主要方法:
- 通过铜(I) 催化亚酸循环添加 (CuAAC) 合成14种erlotinib衍生物.
- 在体外评估使用MTT试验,HepG2和Huh7细胞系的增殖,殖民地形成和迁移试验.
- 通过Bcl-2,切割-caspase3和切割-PARP的西部抹迹来分析亡诱导分析.
- 在体内抗瘤活性和化合物的毒性评估.
主要成果:
- 化合物3c和3d对HepG2和Huh7 HCC细胞系表现出显著的抗瘤疗效.
- 化合物3c和3d抑制了HepG2细胞中的增殖,殖民地形成和迁移,这取决于度.
- 抗瘤活性与亡诱导有关,由Bcl-2下调和分裂酶3/PARP上调证明.
- 化合物3d在体内显示出抗瘤功效,对正常组织有低毒性.
结论:
- 新型的erlotinib衍生物包含1,2,3-triazole部分,对HCC具有强大的抗瘤活性.
- 化合物3d是进一步开发作为肝细胞癌治疗剂的有希望的候选物.
- 观察到的活性是由亡诱导介导的,这为HCC治疗提供了潜在的机制.
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