拉帕蒂尼
喹啉
化学
蛋白激酶B
生存素
IC50型
表皮生长因子受体
表皮生长因子受体抑制剂
细胞毒性
生物信息学
药理学
激酶
癌症研究
体外
生物化学
信号转导
细胞凋亡
癌症
乳腺癌
曲妥珠单抗
受体
生物
基因
遗传学
有机化学
作者
Rasha Z. Batran,Sherien M. El‐Daly,Walaa A. El‐Kashak,Eman Y. Ahmed
摘要
Two series of quinoline-thiazole and quinoline-thiazolidinone hybrids were designed, synthesized, and evaluated for their in vitro antitumor activity on MCF-7 breast cancer cell line. In comparison with lapatinib (IC50 = 4.69 µM), compounds 4b and 6b exhibited the best antiproliferative activity with IC50 values of 33.19 and 5.35 µM, respectively. Although compound 6b showed higher cytotoxicity, compound 4b exhibited better inhibitory activity toward the epidermal growth factor receptor (EGFR) pathway than compound 6b as represented by the significant reduction in the EGFR kinase activity and the levels of phosho-EGFR and phosho-AKT when compared to lapatinib as a reference standard. Moreover, compound 4b was capable of down-regulating the anti-apoptotic genes Bcl-2 and survivin and up-regulating the level of the pro-apoptotic gene BAX. Molecular modeling study was carried out to predict the binding interactions of both compounds into the target kinase. Finally, the physicochemical properties were investigated in silico as well.
科研通智能强力驱动
Strongly Powered by AbleSci AI