Abstract
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 4b, 4j, 4k, and 4e exhibited the most potent cytotoxic activity of IC(50) values (0.002 - 0.004 µM) comparing to Staurosporine of IC(50); 0.005 μM. The latter derivatives exhibited a promising safety profile against the normal human WI38 cells of IC(50) range 0.0149 - 0.048 µM. Furthermore, the most promising cytotoxic compounds 4b, 4j 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(50) values 0.17 × 10(-3), 0.07 × 10(-3) µM in comparison with the reference drug sorafenib of IC(50); 0.28 × 10(-3), 0.13 × 10(-3) µM, respectively. In addition, 4j induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells.