Abd El-Lateef Hany M, Gaafar Ahmed, Alqahtani Arwa Sultan, Al-Mutairi Aamal A, Alshaya Dalal Sulaiman, Elsaid Fahmy Gad, Fayad Eman, Farouk N A
Department of Chemistry, College of Science, King Faisal University Al-Ahsa 31982 Saudi Arabia
Department of Chemistry, Faculty of Science, Sohag University Sohag 82524 Egypt.
RSC Adv. 2024 Aug 7;14(34):24781-24790. doi: 10.1039/d4ra04915b. eCollection 2024 Aug 5.
In this work, a congeneric set of quinoline-tethered -vinyl triamide hybrids was prepared and evaluated as EGFR tyrosine kinase inhibitors for the management of breast cancer. All of the prepared hybrids were evaluated for their antiproliferative effect against the breast MCF-7 cell line. Among the tested hybrids, compound 6f displayed the most potent antiproliferative activity with an IC value of 1.87 μM compared to STU (IC = 13.71 μM) as the standard reference. The most promising hybrid, 6f, was found to induce cellular cycle arrest at the G1 phase. Furthermore, the molecular mechanism of this hybrid revealed its ability to induce cellular apoptosis the mitochondrial-dependent apoptotic pathway. Compound 6f decreased MCF-7 cells' MMP compared to the controls (percentage change value of 57.93%). Further investigation of the selective compound 6f showed that it can inhibit EGFR tyrosine kinase.
在本研究中，制备了一组喹啉连接的β-乙烯基三酰胺同系物杂化物，并将其作为表皮生长因子受体（EGFR）酪氨酸激酶抑制剂用于乳腺癌治疗的评估。对所有制备的杂化物进行了抗乳腺癌MCF-7细胞系增殖作用的评估。在测试的杂化物中，化合物6f表现出最强的抗增殖活性，其IC50值为1.87 μM，而作为标准对照的STU（IC50 = 13.71 μM）。最有前景的杂化物6f被发现可诱导细胞周期停滞于G1期。此外，该杂化物的分子机制显示其具有通过线粒体依赖性凋亡途径诱导细胞凋亡的能力。与对照相比，化合物6f使MCF-7细胞的线粒体膜电位（MMP）降低（百分比变化值为57.93%）。对选择性化合物6f的进一步研究表明，它可以抑制EGFR酪氨酸激酶。
