Mohamed Manar R, Mahmoud Walaa R, Refaey Rana H, George Riham F, Georgey Hanan H
Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Cairo University, El-Kasr El-Eini Street, Cairo 11562, Egypt.
Pharmaceutical Chemistry Department, Faculty of Pharmacy, October University for Modern Sciences and Arts (MSA), Giza 12411, Egypt.
ACS Med Chem Lett. 2024 May 29;15(6):892-898. doi: 10.1021/acsmedchemlett.4c00095. eCollection 2024 Jun 13.
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 (, , , , , , , , , and ) 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 μM, compared with Sorafenib and Sunitinib with IC values of 0.06 and 0.12 μM, respectively. The most promising candidate, , 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.
合成了两个系列的十种新型1,2,4-三取代咪唑啉-5-酮，并针对MCF-7乳腺癌和A549肺癌细胞系进行筛选，以测试它们的体外抗癌活性潜力。结果显示，与A549细胞系相比，受试化合物对MCF-7细胞系具有优先活性。对最有前景的十种化合物（、、、、、、、、和）进行VEGFR-2酶抑制活性测试，以进一步探索其作用机制。受试化合物在0.07至0.36μM的微摩尔浓度范围内显示出显著的酶抑制作用，而索拉非尼和舒尼替尼的IC值分别为0.06和0.12μM。最有前景的候选化合物进一步评估其细胞周期阶段、凋亡诱导能力，以及其抗增殖活性和对内皮细胞迁移的抑制潜力，通过细胞划痕试验进行分析。此外，还进行了计算机模拟研究，以识别和检测结合构象的稳定性。
