Abdel-Maksoud Mohammed S, Mohamed Ahmed A B, Hassan Rasha M, Abdelgawad Mohamed A, Chilingaryan Garri, Selim Samy, Abdel-Bakky Mohamed S, Al-Sanea Mohammad M
Pharmaceutical and Drug Industries Research Division, Medicinal & Pharmaceutical Chemistry Department, National Research Centre (ID: 60014618), Dokki, Giza 12622, Egypt.
Department of Medicinal Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Int J Mol Sci. 2021 Sep 28;22(19):10491. doi: 10.3390/ijms221910491.
A new series of 4-(1-benzo[]imidazol-1-yl)pyrimidin-2-amine linked sulfonamide derivatives was designed and synthesized according to the structure of well-established V600EBRAF inhibitors. The terminal sulfonamide moiety was linked to the pyrimidine ring via either ethylamine or propylamine bridge. The designed series was tested at fixed concentration (1 µM) against V600EBRAF, finding that , and exhibited the strongest inhibitory activity among all target compounds and had the lowest IC of 0.49 µM. They were further screened on NCI 60 cancer cell lines to reveal that showed the most significant growth inhibition against multiple cancer cell lines. Therefore, cell cycle analysis of was conducted to investigate the effect on cell cycle progression. Finally, virtual docking studies was performed to gain insights for the plausible binding modes of vemurafenib, , and .
根据成熟的V600EBRAF抑制剂的结构，设计并合成了一系列新的4-(1-苯并咪唑-1-基)嘧啶-2-胺连接的磺酰胺衍生物。末端磺酰胺部分通过乙胺或丙胺桥连接到嘧啶环上。在固定浓度（1 μM）下对设计的系列化合物针对V600EBRAF进行测试，发现 、 和 在所有目标化合物中表现出最强的抑制活性， 具有最低的IC50，为0.49 μM。它们在NCI 60癌细胞系上进一步筛选，结果显示 对多种癌细胞系表现出最显著的生长抑制作用。因此，对 进行了细胞周期分析，以研究其对细胞周期进程的影响。最后，进行了虚拟对接研究，以深入了解维莫非尼、 、 和 的可能结合模式。
