Othman Dina I A, Hamdi Abdelrahman, Elhusseiny Walaa M, El-Azab Adel S, Bakheit Ahmed H, Hefnawy Mohamed, Abdel-Aziz Alaa A-M
Department of Pharmaceutical Organic Chemistry, Faculty of Pharmacy, Mansoura University, Mansoura 35516, Egypt.
Department of Pharmaceutical Chemistry, College of Pharmacy, P.O. Box 2457, King Saud University, Riyadh 11451, Saudi Arabia.
Saudi Pharm J. 2023 Nov;31(11):101803. doi: 10.1016/j.jsps.2023.101803. Epub 2023 Sep 28.
Spirochromanes incorporating Schiff's bases and semicarbazones and were synthesizedand analyzed for their potential antiproliferative activity using four human cancer cell lines (MCF-7, HCT-116, PC3, and A549). Compounds , and possessed the highest antiproliferative activity among the tested compounds,with an IC range of 1.154-9.09 μM. Compound selectively inhibited the PC3 cell proliferation (IC = 5.47 μM). Spirochromanes , and exhibited high inhibitory activity against EGFR (IC = 0.116, 0.132, and 0.077 μM, respectively) and HER2 (IC = 0.055, 0.210 and 0.085 μM, respectively) compared with the references, erlotinib (IC = 0.090 and 0.038 μM, respectively) and gefitinib (IC = 0.052 and 0.072 μM, respectively). Cell cycle analysis and apoptosis results showed that compounds , and arrested growth inthe S phase, and the programmed cell death induced by these compounds was an apoptotic mechanism rather than a necrotic pathway. Molecular docking studies of spirochromanes , and to EGFR and HER2 binding sites were performed to explore the orientation mode and interaction.
合成了含有席夫碱和缩氨基脲的螺色满，并使用四种人类癌细胞系（MCF - 7、HCT - 116、PC3和A549）分析了它们潜在的抗增殖活性。化合物 、 和 在测试化合物中具有最高的抗增殖活性，IC范围为1.154 - 9.09 μM。化合物 选择性抑制PC3细胞增殖（IC = 5.47 μM）。与对照药厄洛替尼（IC分别为0.090和0.038 μM）和吉非替尼（IC分别为0.052和0.072 μM）相比，螺色满 、 和 对EGFR（IC分别为0.116、0.132和0.077 μM）和HER2（IC分别为0.055、0.210和0.085 μM）表现出高抑制活性。细胞周期分析和凋亡结果表明，化合物 、 和 使细胞生长停滞在S期，这些化合物诱导的程序性细胞死亡是一种凋亡机制而非坏死途径。对螺色满 、 和 与EGFR和HER2结合位点进行了分子对接研究，以探索其取向模式和相互作用。
