期刊
CHEMICAL BIOLOGY & DRUG DESIGN
卷 101, 期 3, 页码 749-759出版社
WILEY
DOI: 10.1111/cbdd.14178
关键词
1; 2; 3-triazole; anticancer; cell cycle; EGFR; viability
A novel series of 1,2,3-triazole/chalcone hybrids were synthesized and evaluated for their cytotoxic activity and EGFR/BRAF inhibitory effects. Compound 6d showed the highest antiproliferative activity and was found to be a potent EGFR inhibitor. Additionally, it exhibited modest BRAF inhibitory action and caused cell cycle arrest at the G1 transition phase.
A novel series of 1,2,3-triazole/chalcone hybrids 6a-n was designed and synthesized using a molecular hybridization approach to develop a new cytotoxic agent capable of targeting epidermal growth factor receptor (EGFR) and/or BRAF. The antiproliferative effect of the novel hybrids was investigated against four cancer cells using doxorubicin as a reference. Hybrids 6a, 6d, 6f-h, and 6n have the highest antiproliferative activity (IC50 values 0.95-1.80 mu M) compared to doxorubicin (IC50 1.14 mu M). The most potent antiproliferative derivative, compound 6d, was also the most potent EGFR inhibitor with an IC50 of 0.09 +/- 0.05 mu M, which is comparable to the reference Erlotinib (IC50 = 0.05 +/- 0.03 mu M). 6d has modest BRAF inhibitory action with an IC50 of 0.90 +/- 0.10 mu M. The findings were also related to molecular docking studies, which provided models of strong interactions with the EGFR-TK domain for the inhibitors. In cell cycle analysis, hybrid 6d caused a cell cycle arrest at the G1 transition phase.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据