Abd El-Lateef Hany M, Bafail Duaa, Alhalees Noura Hamdi Yousef, Toson Eslam E M, Abu Almaaty Ali H, Elsayed Elsherbiny H, Zaki Islam, Youssef Magdy M
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 Jul 26;14(32):23495-23504. doi: 10.1039/d4ra03963g. eCollection 2024 Jul 19.
Novel derivatives of the 2-(quinoline-4-carbonyl)hydrazide scaffold carrying the acrylamide moiety were synthesized and tested for their cytotoxic efficacy against the breast carcinoma MCF-7 cell line. The most active members 6a, 6b and 6h revealed significant antiproliferative action with an IC value of 3.39, 5.94 and 2.71 μM, respectively, which were more potent than the reference drug Dox (IC = 6.18 μM). Aiming to enlighten the antiproliferative activity, compounds 6a and 6h were examined for their inhibitory potential against EGFR kinase. The results demonstrated that compound 6h displayed potent inhibitory activity, as concluded from the IC value (IC = 0.22 μM) compared to the standard drug Lapatinib (IC value of 0.18 μM). Compound 6h was found to induce significant cellular cycle arrest at the G1 phase and provoke apoptosis. Besides, compound 6h triggered apoptosis upregulating p53 and initiator caspase 9 by 7.4- and 8.7-fold, respectively, compared to DMSO controls.
合成了带有丙烯酰胺部分的2-(喹啉-4-羰基)酰肼支架的新型衍生物，并测试了它们对乳腺癌MCF-7细胞系的细胞毒性功效。活性最强的成员6a、6b和6h显示出显著的抗增殖作用，IC值分别为3.39、5.94和2.71 μM，比参考药物多柔比星（Dox，IC = 6.18 μM）更有效。为了阐明抗增殖活性，研究了化合物6a和6h对表皮生长因子受体（EGFR）激酶的抑制潜力。结果表明，与标准药物拉帕替尼（IC值为0.18 μM）相比，化合物6h从IC值（IC = 0.22 μM）得出显示出强效抑制活性。发现化合物6h在G1期诱导显著的细胞周期停滞并引发细胞凋亡。此外，与二甲基亚砜（DMSO）对照相比，化合物6h分别使p53和起始半胱天冬酶9上调7.4倍和8.7倍，从而引发细胞凋亡。
