Chemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia.
Chemistry Department, Faculty of Science, Albaha University, Albaha, Saudi Arabia.
J Enzyme Inhib Med Chem. 2021 Dec;36(1):1454-1471. doi: 10.1080/14756366.2021.1944126.
A new set of 4,6,7,8-tetrahydroquinolin-5(1H)-ones were designed as cytotoxic agents against breast cancer cell line (MCF-7) and synthesised under ultrasonic irradiation using chitosan decorated copper nanoparticles (CS/CuNPs) catalyst. The new compounds , , , and exhibited the most potent cytotoxic activity of IC values (0.002 - 0.004 µM) comparing to Staurosporine of IC; 0.005 μM. The latter derivatives exhibited a promising safety profile against the normal human WI38 cells of IC range 0.0149 - 0.048 µM. Furthermore, the most promising cytotoxic compounds , were evaluated as multi-targeting agents against the RTK protein kinases; EGFR, HER-2, PDGFR-β, and VEGFR-2. Compound 4j showed promising inhibitory activity against HER-2 and PDGFR-β of IC values 0.17 × 10, 0.07 × 10 µM in comparison with the reference drug sorafenib of IC; 0.28 × 10, 0.13 × 10 µM, respectively. In addition, induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells.
一组新的 4,6,7,8-四氢喹啉-5(1H)-酮被设计为针对乳腺癌细胞系（MCF-7）的细胞毒性剂，并在超声辐射下使用壳聚糖修饰的铜纳米粒子（CS/CuNPs）催化剂合成。与 IC 值为 0.005 μM 的 Staurosporine 相比，新化合物 、 、 和 表现出最强的细胞毒性活性，IC 值为 0.002-0.004 μM。这些衍生物对正常人类 WI38 细胞表现出有希望的安全性，IC 值范围为 0.0149-0.048 μM。此外，最有前途的细胞毒性化合物 、 被评估为针对 RTK 蛋白激酶的多靶点药物；EGFR、HER-2、PDGFR-β 和 VEGFR-2。化合物 4j 对 HER-2 和 PDGFR-β 的抑制活性表现出良好的抑制活性，IC 值分别为 0.17×10 和 0.07×10 μM，而参考药物索拉非尼的 IC 值分别为 0.28×10 和 0.13×10 μM。此外， 诱导 MCF-7 细胞中的凋亡作用和细胞周期停滞在 G2/M 期，阻止有丝分裂周期。
