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
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) wer...
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| Main Authors: | , , , , , |
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| Format: | Article |
| Language: | English |
| Published: |
Nature Portfolio
2025-07-01
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| Series: | Scientific Reports |
| Subjects: | |
| Online Access: | https://doi.org/10.1038/s41598-025-12140-1 |
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| Summary: | 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. |
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| ISSN: | 2045-2322 |