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<p>Quinazolinone derivatives have been broadly studied as anti-cancer drug candidates due to their potential to inhibit key signaling pathways involved in tumor progression. In the current study, new 2-[(4-substituted-5-methylfuran-3-yl)thio]-3-phenylquinazolin-4(3<i>H</i>)-one derivatives (<b>2</b>–<b>10</b>) were designed and assessed for anti-cancer activity. Cytotoxicity of the compounds was tested against normal WI-38 cells and cancer cell lines HepG-2 (liver), MCF-7 (breast), and HCT-116 (colorectal). In addition, their inhibitory effects on EGFR and VEGFR-2, key targets for tumor growth and angiogenesis, were assessed. Compounds <b>6b</b> and <b>10</b> showed significant cytotoxic activity, with<b> 6b</b> (IC₅₀ = 0.19 ± 0.03&#xa0;μM) being the most effective EGFR inhibitor, over <b>10</b> (IC₅₀ = 0.51 ± 0.04&#xa0;μM) and as potent as erlotinib (IC₅₀ = 0.23 ± 0.02&#xa0;μM). Flow cytometry revealed that <b>6b</b> induced apoptosis in 35.29% of MCF-7 cells and G₂/M phase cell cycle arrest, much better than that of untreated cells (6.81%). In silico ADMET prediction and molecular docking confirmed high EGFR binding affinity and favorable pharmacokinetic properties. Overall, compound <b>6b</b> showed promising anti-cancer activity via EGFR inhibition, apoptosis, and cell cycle arrest and is a good lead for further development as an EGFR-targeted agent.</p>

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Design, antiproliferative potency, and in silico studies of novel 5-methylfuran-3-yl)thio)-3-phenylquinazolin-4(3H)-one based derivatives as potential EGFR inhibitors

  • 期刊论文

  • 出版模式：

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  • 发表日期：

    2025年7月31日

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  • Sara M. Soliman,
  • Adel A.-H. Abdel-Rahman,
  • Eman S. Nossier,
  • Modather F. Hussein,
  • Amr Sabry,
  • Hagar S. El-Hema

摘要

Quinazolinone derivatives have been broadly studied as anti-cancer drug candidates due to their potential to inhibit key signaling pathways involved in tumor progression. In the current study, new 2-[(4-substituted-5-methylfuran-3-yl)thio]-3-phenylquinazolin-4(3H)-one derivatives (2–10) were designed and assessed for anti-cancer activity. Cytotoxicity of the compounds was tested against normal WI-38 cells and cancer cell lines HepG-2 (liver), MCF-7 (breast), and HCT-116 (colorectal). In addition, their inhibitory effects on EGFR and VEGFR-2, key targets for tumor growth and angiogenesis, were assessed. Compounds 6b and 10 showed significant cytotoxic activity, with 6b (IC₅₀ = 0.19 ± 0.03 μM) being the most effective EGFR inhibitor, over 10 (IC₅₀ = 0.51 ± 0.04 μM) and as potent as erlotinib (IC₅₀ = 0.23 ± 0.02 μM). Flow cytometry revealed that 6b induced apoptosis in 35.29% of MCF-7 cells and G₂/M phase cell cycle arrest, much better than that of untreated cells (6.81%). In silico ADMET prediction and molecular docking confirmed high EGFR binding affinity and favorable pharmacokinetic properties. Overall, compound 6b showed promising anti-cancer activity via EGFR inhibition, apoptosis, and cell cycle arrest and is a good lead for further development as an EGFR-targeted agent.