埃罗替尼
化学
广告
表皮生长因子受体抑制剂
生物信息学
嘧啶
表皮生长因子受体
对接(动物)
蛋白质数据库
IC50型
体外
噻唑烷
立体化学
激酶
药理学
组合化学
生物化学
受体
医学
护理部
基因
作者
Sandhya Rani Bandi,Ravikumar Kapavarapu,Rambabu Palabindela,Mohammad Azam,Min Kim,Sirassu Narsimha
标识
DOI:10.1016/j.molstruc.2023.136451
摘要
In this study, we designed and synthesized a number of novel pyrido[2,3-d]pyrimidine-thiazolidine-1,2,3-triazole derivatives and investigated them in vitro for their inhibitory action toward EGFR kinases and anti-proliferative activity against two different cell lines. When compared to the lead chemical, erlotinib, the majority of the compounds demonstrated acceptable activity. Among them, the most promising compounds 4d and 4e exhibited excellent anti-proliferative activity against the MCF-7 cancer cell line with IC50 values of 4.19 ± 0.24 and 3.52 ± 0.12 µM, respectively, as well as excellent kinase inhibitory activities (EGFR: IC50 = 0.53 ± 0.02 and 0.39 ± 0.03 µM). In silico docking studies were performed to evaluate the molecular interactions of 4a-4o compounds with the human epidermal growth factor receptor, EGFR (PDB: 1M17) proteins with a co-crystallized ligand (erlotinib) and observed that four of the compounds (4d, 4e, 4m, and 4o) had appreciable binding energies compared to the standard drug erlotinib. Finally, the in silico pharmacokinetic profile was predicted for potent compounds 4d, 4e, 4m, and 4o using SWISS/ADME, where the 4m and 4o compounds had a better profile compared to the 4d and 4e compounds.
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