Design and green synthesis of novel quinolinone derivatives of potential anti-breast cancer activity against MCF-7 cell line targeting multi-receptor tyrosine kinases.

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.