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 4b, 4j, 4k, and 4e exhibited the most potent cytotoxic activity of IC50 values (0.002 - 0.004 mu M) comparing to Staurosporine of IC50; 0.005 mu M. The latter derivatives exhibited a promising safety profile against the normal human WI38 cells of IC50 range 0.0149 - 0.048 mu M. Furthermore, the most promising cytotoxic compounds 4b, 4j were evaluated as multi-targeting agents against the RTK protein kinases; EGFR, HER-2, PDGFR-beta, and VEGFR-2. Compound 4j showed promising inhibitory activity against HER-2 and PDGFR-beta of IC50 values 0.17 x 10(-3), 0.07 x 10(-3) mu M in comparison with the reference drug sorafenib of IC50; 0.28 x 10(-3), 0.13 x 10(-3) mu M, respectively. In addition, 4j induced apoptotic effect and cell cycle arrest at G2/M phase preventing the mitotic cycle in MCF-7 cells.