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Updated: Jun 20, 2026
Facile Preparation of 4-Substituted Quinazoline Derivatives
Published on: February 15, 2016
Design, Synthesis of Novel Quinazolinone Derivatives and Evaluation of EGFR Kinase Inhibition Activity via In Vitro
Aybüke Züleyha Kaya1,2, Asaf Evrim Evren1, Gülşen Akalın-Çiftçi3
1Faculty of Pharmacy, Department of Pharmaceutical Chemistry, Anadolu University, Eskisehir, Turkey.
Abstract:
Cancer is one of the most seen diseases worldwide. Due to the serious side effects of anticancer drugs and toxic effects on healthy cells, investigations for novel anticancer agents with low side effects have become one of the most important research areas of our age. With this objective, 17 new compounds were designed and successfully synthesized based on the quinazolinone, which is commonly found in the structures of FDA-approved EGFR inhibitors, and their structures were elucidated by IR, HRMS, 1H, and 13C-NMR spectral analysis methods. According to cytotoxicity test results, it was determined that compound 4j showed high inhibitory activity compared to cisplatin and gefitinib in the A549 cell line. In apoptosis induction studies, it was observed that compounds 4a, 4b, 4d, and 4f showed activity in the A549 cell line, while compound 4j showed activity in the MCF-7 cell line. In the study investigating caspase-3 activation, compounds 4a, 4m, and 4o were found active in the A549 cell line, while compounds 4a and 4o were found active in MCF-7 cells. In EGFR enzyme inhibition studies, it was observed that the activities of molecules 4b, 4f, and 4j were higher than gefitinib. In silico studies indicated that 4j interacted by establishing significant bonds with both caspase-3 and EGFR enzyme.
Insights
Researchers developed novel quinazolinone-based compounds as potential anticancer agents. Compound 4j demonstrated significant inhibitory activity against A549 lung cancer cells and interacted with key cancer-related enzymes.
Area of Science:
- Medicinal Chemistry
- Oncology
- Drug Discovery
Background:
- Cancer remains a leading global health concern.
- Conventional chemotherapy exhibits severe side effects and toxicity to healthy cells.
- Developing novel anticancer agents with improved efficacy and reduced toxicity is a critical research priority.
Purpose of the Study:
- To design and synthesize novel quinazolinone derivatives as potential anticancer agents.
- To evaluate the cytotoxic and apoptosis-inducing activities of synthesized compounds.
- To investigate their inhibitory effects on EGFR enzyme and caspase-3 activation.
Main Methods:
- Synthesis of 17 new quinazolinone-based compounds.
- Structural elucidation using IR, HRMS, 1H, and 13C-NMR spectroscopy.
- In vitro cytotoxicity assays (A549, MCF-7 cell lines), apoptosis induction studies, caspase-3 activation assays, and EGFR enzyme inhibition assays.
- In silico molecular docking studies.
Main Results:
- Compound 4j exhibited potent cytotoxicity against A549 cells, outperforming cisplatin and gefitinib.
- Compounds 4a, 4b, 4d, 4f, and 4j demonstrated apoptosis-inducing activity in cancer cell lines.
- Compounds 4a, 4m, and 4o activated caspase-3 in A549 cells.
- Compounds 4b, 4f, and 4j showed superior EGFR enzyme inhibition compared to gefitinib.
- In silico analysis revealed significant interactions of compound 4j with both caspase-3 and EGFR.
Conclusions:
- The synthesized quinazolinone derivatives hold promise as novel anticancer therapeutics.
- Compound 4j is a particularly promising candidate due to its broad-spectrum activity and interaction with key cancer targets.
- Further investigation into these compounds could lead to the development of more effective cancer treatments.
