2. Academic Validation
  3. 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

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

  • Sci Rep. 2025 Jul 31;15(1):27992. doi: 10.1038/s41598-025-12140-1.
Sara M Soliman 1,  Adel A-H Abdel-Rahman 2,  Eman S Nossier 3 4,  Modather F Hussein 5,  Amr Sabry 6,  Hagar S El-Hema 7
Affiliations

Affiliations

  • 1 Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, 32511, Egypt.
  • 2 Chemistry Department, Faculty of Science, Menoufia University, Shebin El-Kom, 32511, Egypt. adelnassar63@yahoo.com.
  • 3 Department of Pharmaceutical Medicinal Chemistry and Drug Design, Faculty of Pharmacy (Girls), Al-Azhar University, Cairo, 11754, Egypt. dr.emannossier@gmail.com.
  • 4 The National Committee of Drugs, Academy of Scientific Research and Technology, Cairo, 11516, Egypt. dr.emannossier@gmail.com.
  • 5 Chemistry Department, College of Science, Jouf University, 72341, Sakaka, Aljouf, Saudi Arabia.
  • 6 Department of Pharmaceutical Manufacturing, Faculty of Pharmacy, MUST University, Giza, 3237101, Egypt.
  • 7 Basic Science Department (Chemistry), Thebes Higher Institute for Engineering, Thebes Academy, Maadi, 11434, Egypt. hagarsabry.23@yahoo.com.
PMID: 40745188 DOI: 10.1038/s41598-025-12140-1
Abstract

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.

Keywords

ADMET; Anticancer; EGFR; Molecular docking; Quantum calculations; Quinazolin-4-one.

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