Insight on Some Newly Synthesized Trisubstituted Imidazolinones as VEGFR-2 Inhibitors

被引：1
作者：
Mohamed, Manar R. [1 ]
Mahmoud, Walaa R. [1 ]
Refaey, Rana H. [2 ]
George, Riham F. [1 ]
Georgey, Hanan H. [1 ,3 ]
机构：
[1] Cairo Univ, Fac Pharm, Dept Pharmaceut Chem, Cairo 11562, Egypt
[2] October Univ Modern Sci & Arts MSA, Fac Pharm, Pharmaceut Chem Dept, Giza 12411, Egypt
[3] Egyptian Chinese Univ, Fac Pharm & Drug Technol, Dept Pharmaceut Chem, Cairo 19346, Egypt
来源：
ACS MEDICINAL CHEMISTRY LETTERS | 2024年 / 15卷 / 06期
关键词：
Imidazolinones; Anticancer; VEGFR-2; inhibitors; Molecular dynamics; ANTICANCER EVALUATION; CARBONIC-ANHYDRASE; KINASE INHIBITORS; DERIVATIVES; SULFONAMIDE; DESIGN;
D O I：
10.1021/acsmedchemlett.4c00095
中图分类号：
R914 [药物化学];
学科分类号：
100701 ;
摘要：
Two series of ten new 1,2,4-trisubstituted imidazolin-5-ones were synthesized and screened against MCF-7 breast cancer and A549 lung cancer cell lines to test their potential in vitro anticancer activity. The results revealed preferential activity of the tested compounds toward MCF-7 cell lines compared to A549 cell lines. The most promising ten compounds (3a, 3c, 3f, 3g, 3h, 3i, 3j, 6a, 6f, and 6i) were subjected to VEGFR-2 enzyme inhibitory activity testing to further explore their mechanism of action. The tested compounds showed remarkable enzyme inhibition in micromolar concentrations ranging from 0.07 to 0.36 mu M, compared with Sorafenib and Sunitinib with IC50 values of 0.06 and 0.12 mu M, respectively. The most promising candidate, 3j, was further evaluated for its cell cycle phases, apoptotic induction ability, as well as its antiproliferative activity and inhibitory potential for endothelial cell migration, analyzed by a cell scratch assay. Furthermore, in silico studies were also performed to identify and detect the stability of the binding poses.
引用
收藏
页码：892 / 898
页数：7
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