Design and green synthesis of novel quinolinone derivatives of potential anti-breast cancer activity against MCF-7 cell line targeting multi-receptor tyrosine kinases |
| |
| Authors: | Mohamed Mokhtar Khadijah S Alghamdi Nesreen S Ahmed Dina Bakhotmah Tamer S Saleh |
| |
| Institution: | aChemistry Department, Faculty of Science, King Abdulaziz University, Jeddah, Saudi Arabia;bChemistry Department, Faculty of Science, Albaha University, Albaha, Saudi Arabia;cDepartment of Therapeutic Chemistry, National Research Centre, Cairo,Egypt;dDepartment of Chemistry, University of Jeddah, College of Science, Jeddah, Saudi Arabia;eGreen Chemistry Department, National Research Centre, Giza, Egypt |
| |
| 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 IC50 values (0.002 − 0.004 µM) comparing to Staurosporine of IC50; 0.005 μM. The latter derivatives exhibited a promising safety profile against the normal human WI38 cells of IC50 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 IC50 values 0.17 × 10−3, 0.07 × 10−3 µM in comparison with the reference drug sorafenib of IC50; 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. |
| |
| Keywords: | 4 6 7 8-Tetrahydroquinolin-5(1H)-one HER-2 inhibitors breast cancer apoptosis molecular docking study |
|
|
