Department of Drug Radiation Research, National Center for Radiation Research and Technology (NCRRT), Egyptian Atomic Energy Authority (EAEA), Cairo, Egypt.
Department of Pharmacognosy, College of Pharmacy, Prince Sattam Bin Abdulaziz University, Al-Kharj, Saudi Arabia.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):218-237. doi: 10.1080/14756366.2020.1854243.
A set of quinazolinones synthesized by the aid of L-norephedrine was assembled to generate novel analogues as potential anticancer and radiosensitizing agents. The new compounds were evaluated for their cytotoxic activity against MDA-MB-231, MCF-7, HepG-2, HCT-116 cancer cell lines and EGFR inhibitory activity. The most active compounds and were screened against MCF-10A normal cell line and displayed lower toxic effects. They proved their relative safety with high selectivity towards MDA-MB-231 breast cancer cell line. Measurement of the radiosensitizing activity for and revealed that they could sensitize the tumour cells after being exposed to a single dose of 8 Gy gamma radiation. Compound was able to induce apoptosis and arrest the cell cycle at the G2-M phase. Molecular docking of and in the active site of EGFR was performed to gain insight into the binding interactions with the key amino acids.
一套由 L-去甲肾上腺素辅助合成的喹唑啉酮被组装起来，生成新的类似物作为潜在的抗癌和放射增敏剂。评估了新化合物对 MDA-MB-231、MCF-7、HepG-2、HCT-116 癌细胞系的细胞毒性活性和 EGFR 抑制活性。最活性化合物 和 对 MCF-10A 正常细胞系进行了筛选，显示出较低的毒性作用。它们对 MDA-MB-231 乳腺癌细胞系具有较高的选择性，证明了它们相对安全。对 和 的放射增敏活性的测量表明，它们可以在暴露于 8Gyγ射线的单次剂量后使肿瘤细胞敏感。化合物 能够诱导细胞凋亡并将细胞周期阻滞在 G2-M 期。对 EGFR 活性位点的 和 进行了分子对接，以深入了解与关键氨基酸的结合相互作用。
