Synthesis, anticancer and apoptosis-inducing activities of quinazoline–isatin conjugates: epidermal growth factor receptor-tyrosine kinase assay and molecular docking studies

Abstract

A new series of quinazolinone compounds 16–34 incorporating isatin moieties was synthesized. The antitumor efficacy of the compounds against MDA-MB-231, a breast cancer cell line, and LOVO, a colon cancer cell line, was assessed. Compounds 20, 21, 22, 23, 25, 27, 28, 29, 30, 31, 32, 33, and 34 displayed potent antitumor activity against MDA-MB-231 and LOVO cells (IC₅₀: 10.38–38.67 μM and 9.91–15.77 μM, respectively); the comparative IC₅₀ values for 5-fluorouracil and erlotinib in these cells lines were 70.28 μM, 22.24 μM and 15.23 μM, 25.31 μM respectively. The EGFR-TK assay and induction of apoptosis for compound 31 were investigated to assess its potential cytotoxic activity as a representative example of the novel synthesized compounds. At a concentration of 10 μM, compound 31 exhibited efficient inhibitory effect against EGFR-TK and induced apoptosis in MDA-MB-231 cells. Furthermore, a molecular docking study for compound 31 and erlotinib was performed to verify the binding mode toward the EGFR kinase enzyme, and showed a similar interaction as that with erlotinib alone.

Graphical Abstract: Compound 31 showed potent antitumor activity and efficient inhibitory effect against EGFR-TK and induced apoptosis of MDA-MB-231 cells at a concentration of 10 μM.

Graphical Abstract

Keywords:

• Synthesis
• isatin
• quinazolinone
• antitumor
• EGFR-TK
• molecular docking

Additional information

Funding

The authors extend their appreciation to the Deanship of Scientific Research at King Saud University for funding the work through the research group project No. RG-1435-046.