招募六氢喹啉作为抗癌支架，针对抑制野生型和突变型 EGFR（EGFR、EGFR 和 EGFR）。

Recruitment of hexahydroquinoline as anticancer scaffold targeting inhibition of wild and mutants EGFR (EGFR, EGFR, and EGFR).

机构信息

Department of Pharmaceutical Chemistry, Faculty of Pharmacy, Tanta University, Tanta, Egypt.

Pharmaceutical Chemistry Department, College of Pharmacy, Umm Al-Qura University, Makkah, Saudi Arabia.

出版信息

J Enzyme Inhib Med Chem. 2023 Dec;38(1):2241674. doi: 10.1080/14756366.2023.2241674.

Hexahydroquinoline (HHQ) scaffold was constructed and recruited for development of new series of anticancer agents. Thirty-two new compounds were synthesised where x-ray crystallography was performed to confirm enantiomerism. Thirteen compounds showed moderate to good activity against NCI 60 cancer cell lines, with GI % mean up to 74% for . Expending erlotinib as a reference drug, target compounds were verified for their inhibiting activities against EGFR, EGFR, and EGFR where compound was the best inhibitor with IC = 0.097, 0.280, and 0.051 µM, respectively, compared to erlotinib (IC = 0.082 µM, 0.342 µM, and 0.055 µM, respectively). Safety profile was validated using normal human lung (IMR-90) cells. and disrupted cell cycle at pre-G1 and G2/M phases in lung cancer, HOP-92, and cell line. Molecular docking study was achieved to understand the potential binding interactions and affinities in the active sites of three versions of EGFRs.

六氢喹啉（HHQ）支架被构建并用于开发一系列新的抗癌药物。合成了 32 种新化合物，其中进行了 X 射线晶体学以确认对映异构体。其中 13 种化合物对 NCI 60 癌细胞系表现出中等至良好的活性，GI%平均值高达 74%。以厄洛替尼作为参考药物，验证了目标化合物对 EGFR、EGFR 和 EGFR 的抑制活性，其中化合物是最好的抑制剂，IC = 0.097、0.280 和 0.051μM，分别与厄洛替尼（IC = 0.082μM、0.342μM 和 0.055μM）相比。使用正常人类肺（IMR-90）细胞验证了安全性概况。化合物和在肺癌、HOP-92 和细胞系中使细胞周期在 G1 期和 G2/M 期前中断。进行了分子对接研究，以了解三种 EGFR 版本的活性部位的潜在结合相互作用和亲和力。