Design, synthesis, biological evaluation, and molecular docking of novel quinazolinone EGFR inhibitors as targeted anticancer agents

A novel series of 2-methyl-3-phenylquinazolin-4-one derivatives were synthesized and biologically evaluated for their cytotoxic potential against MCF-7, HepG2, and PC-3 cancer cells. Most of the tested compounds showed reasonable safety in the normal human skin melanocyte HFB4 cell line. Compound 4...

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Bibliographic Details
Published in:Synthetic communications 2022-09, Vol.52 (18), p.1805-1824
Main Authors: Nofal, Zinab M., Amin, Kamelia M., Mohamed, Hanaa S., El-Kerdawy, Ahmed M., Aly, Magdy S., Habib, Basma S., Sarhan, Alaadin E.
Format: Article
Language:English
Subjects:
Anticancer properties
Cell division
Chemical synthesis
Cytotoxicity
EGFR
MCF-7
Molecular docking
quinazolinone
Toxicity
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Summary:A novel series of 2-methyl-3-phenylquinazolin-4-one derivatives were synthesized and biologically evaluated for their cytotoxic potential against MCF-7, HepG2, and PC-3 cancer cells. Most of the tested compounds showed reasonable safety in the normal human skin melanocyte HFB4 cell line. Compound 4 showed potent cytotoxicity on Hep-G2 cell lines, while compound 9 showed potent cytotoxicity on the MCF-7 cell line, whereas compounds 10 and 12 showed potent cytotoxicity on Hep-G2 cell lines using 5-fluorouracil as a reference standard. Cell division analysis on the tested cell lines revealed that compounds 4, 9, 10, and 12 have potent antiproliferative properties. An in vitro enzymatic inhibition assay against EGFR-TK confirmed that those compounds have potent EGFR inhibitory activity. The target compounds arrested the cell cycle at the pre-G1 and G2/M phases. Molecular docking simulations showed that all the target compounds possess a common binding pattern like that of Erlotinib.
ISSN:0039-7911
1532-2432
DOI:10.1080/00397911.2022.2114373