Yenigun Vildan Betul, Guler Eray Metin, Kocyigit Abdurrahim, Ökten Salih, Balkan Ezgi, Çakmak Osman
Bezmialem Vakıf University, Faculty of Medicine, Department of Medical Biochemistry, Istanbul, Türkiye.
Bezmialem Vakif University, Vocational School of Health Services, Istanbul, Türkiye.
Cell Biochem Biophys. 2025 Jun 10. doi: 10.1007/s12013-025-01793-4.
The heterocyclic aromatic compound quinoline is widely used in pharmaceutical production due to its diverse biological activities, including anticancer properties. This study aimed to investigate the anticancer properties of newly synthesized quinoline derivatives: 5,7-dibromo-8-hydroxyquinoline (MC-5-2), 6,8-dibromotetrahydroquinoline (SO-3-3), nitroquinoline bromide (SO-22), and methoxyhydroxyquinoline bromide (SO-18) against breast cancer. Cytotoxic, genotoxic, apoptotic, and oxidative stress effects were assessed through ATP viability, comet, AO/EB staining, and H2DCF-DA assays using MCF-7 and MDA-MB-231 cancer cells and normal 184A1 breast epithelial cells. Intracellular glutathione levels were analyzed using the luminometric method using a GSH kit, and mitochondrial membrane potential through DiOC6(3) dye. ATP cell viability assay revealed significant reductions in cancer cell vitality with a lower impact on normal cells. MC-5-2 exhibited the highest cytotoxicity on MDA-MB-231 breast cancer cells, with the lowest IC value. Synthesized quinoline derivatives exhibited higher genotoxic and apoptotic effects through iROS-generating activity in a dose-dependent manner against breast cancer cells than the normal breast epithelial cells. Furthermore, quinoline derivatives disrupted mitochondrial membrane potential (ΔΨm) and reduced intracellular glutathione (GSH) levels, with MC-5-2 demonstrating the most substantial effects. These findings suggest that the newly synthesized quinoline derivatives, particularly MC-5-2, possess potent anticancer properties with a favorable selectivity profile.
杂环芳香化合物喹啉因其多样的生物活性，包括抗癌特性，而被广泛应用于药物生产。本研究旨在探究新合成的喹啉衍生物：5,7-二溴-8-羟基喹啉（MC-5-2）、6,8-二溴四氢喹啉（SO-3-3）、硝基喹啉溴化物（SO-22）和甲氧基羟基喹啉溴化物（SO-18）对乳腺癌的抗癌特性。使用MCF-7和MDA-MB-231癌细胞以及正常的184A1乳腺上皮细胞，通过ATP活力、彗星实验、AO/EB染色和H2DCF-DA检测评估细胞毒性、遗传毒性、凋亡和氧化应激效应。使用GSH试剂盒通过荧光法分析细胞内谷胱甘肽水平，并通过DiOC6(3)染料检测线粒体膜电位。ATP细胞活力检测显示癌细胞活力显著降低，对正常细胞的影响较小。MC-5-2对MDA-MB-231乳腺癌细胞表现出最高的细胞毒性，IC值最低。合成的喹啉衍生物通过诱导活性氧生成，以剂量依赖的方式对乳腺癌细胞表现出比正常乳腺上皮细胞更高的遗传毒性和凋亡效应。此外，喹啉衍生物破坏线粒体膜电位（ΔΨm）并降低细胞内谷胱甘肽（GSH）水平，其中MC-5-2的作用最为显著。这些发现表明，新合成的喹啉衍生物，特别是MC-5-2，具有强大的抗癌特性和良好的选择性。
