A number of NO-releasing quinoline derivatives have been designed and synthesized by introducing NO donor to quinoline carboxylic acid fragment. The anti-proliferation of all target compounds was evaluated against human cancer cell lines (HCT-116, MCF-7, and A549), MCF-7/ADR and normal cell (MCF-10A). Most compounds showed cytotoxic activity on cancer cells and drug-resistant cells with IC₅₀ values in the range of 0.62–5.51 μM. Importantly, these compounds showed low toxicity to normal cells (4.21–34.08 μM). Further mechanism studies showed that the most potent compound 9 could release high concentration of NO and inhibit the activity of topoisomerase I. In addition, 9 regulated apoptosis-related proteins, generated ROS and blocked MCF-7 cells in G2/M phase to induce cell apoptosis. Furthermore, the P-gp-mediated transport was also influenced by 9. And 9 could significantly inhibit the growth of tumor in vivo without observable organ-related toxicities. Overall, as a novel NO-releasing quinoline derivative, 9 was worthy for further in-depth study.

通过将NO供体引入喹啉羧酸片段，设计并合成了许多释放NO的喹啉衍生物。所有目标化合物的抗增殖作用均针对人类癌细胞系（HCT-116、MCF-7 和 A549）、MCF-7/ADR 和正常细胞（MCF-10A）进行了评估。大多数化合物对癌细胞和耐药细胞表现出细胞毒活性，IC ₅₀值在0.62–5.51 μM 范围内。重要的是，这些化合物对正常细胞表现出低毒性（4.21–34.08 μM）。进一步的机制研究表明，最强效的化合物9可以释放高浓度的NO并抑制拓扑异构酶I的活性。此外， 9还调节凋亡相关蛋白，产生ROS并阻断MCF-7细胞处于G2/M期，诱导细胞凋亡。细胞凋亡。此外，P-gp 介导的转运也受到9 的影响。 9可显着抑制体内肿瘤的生长，且未观察到与器官相关的毒性。总体而言， 9作为一种新型的释放NO的喹啉衍生物，值得进一步深入研究。