化学
赫拉
细胞毒性
表皮生长因子受体抑制剂
MTT法
连接器
癌细胞
对接(动物)
表皮生长因子受体
细胞凋亡
受体酪氨酸激酶
吲哚试验
细胞毒性T细胞
激酶
立体化学
生物化学
药理学
受体
癌症
体外
生物
医学
护理部
计算机科学
遗传学
操作系统
作者
Mustafa M. Allawi,Ammar A. Razzak Mahmood,Lubna H. Tahtamouni,Mai F. AlSakhen,Sami B. Kanaan,Khaled Saleh,Salem R. Yasin
标识
DOI:10.1002/cbdv.202301892
摘要
Epidermal growth factor receptor (EGFR) and vascular endothelial growth factor receptor (VEGFR) are commonly overexpressed in cancers making them appealing targets for cancer therapeutics. Two groups of indole-6-carboxylic acid derivatives, hydrazone derivatives targeting EGFR and oxadiazole derivatives targeting VEGFR-2, were synthesized and characterized using FT-IR, 1 H-NMR, 13 CNMR, and HR-MS techniques. Binding patterns to potential molecular targets were studied using molecular docking and compared to standard EGFR and VEGFR-2 inhibitors. The newly synthesized compounds were cytotoxic to the three cancer cell lines tested (HCT-116, HeLa, and HT-29 cell lines) as evaluated by the MTT assay. Compound 3 b (EGFR-targeting) and compound 6 e (VEGFR-2-targeting) possessed the highest antiproliferation activity, were cancer-selective, arrested cancer cells in the G2/M phase, induced the extrinsic apoptosis pathway, and had the highest EGFR/VEGFR-2 enzyme inhibitory activity, respectively. The structure-activity relationships of the new compounds showed that the presence of an aryl or heteroaryl fragment attached to a linker is required for the anti-tumor activity. In conclusion, the findings of the current study suggest that compounds 3 b and 6 e are promising cytotoxic agents that act by inhibiting EGFR and VEGFR-2 tyrosine kinases, respectively.
科研通智能强力驱动
Strongly Powered by AbleSci AI