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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...

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Bibliographic Details
Published in:Journal of enzyme inhibition and medicinal chemistry 2021-01, Vol.36 (1), p.1453-1470
Main Authors: Mokhtar, Mohamed, Alghamdi, Khadijah S., Ahmed, Nesreen S., Bakhotmah, Dina, Saleh, Tamer S.
Format: Article
Language:English
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Summary: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.
ISSN:1475-6366
1475-6374
DOI:10.1080/14756366.2021.1944126