Design, synthesis, structural characterization and in - vitro anticancer evaluation of novel quinazolinone derivatives

A series of novel 3 - methyl quinazolinone derivatives were synthesized and evaluated for their anticancer activity. The compounds were prepared through a cyclization reaction of anthranilic acid, followed by nucleophilic substitution with substituted anilin es. The structures of the derivatives were confirmed using FT - IR, NMR, and mass spectrometry. The anticancer activity was tested against a panel of human cancer cell lines, including A549 (lung carcinoma), MCF - 7 (breast cancer), HeLa (cervical cancer), PC - 3 (prostate cancer), and SMMC - 7721 (liver cancer) using the MTT assay. Among the synthesized compounds, several derivatives showed significant cytotoxic activity, with compounds 5g, 5k, and 5l exhibiting the highest potency. Notably, compound 5k demonstrat ed potent inhibition of EGFRwt - TK (epidermal growth factor wild - type tyrosine kinase) with an IC₅₀ of 10 nM. Furthermore, compound 5k induced late - stage apoptosis and caused G2/M phase cell cycle arrest in A549 cells, suggesting its mechanism of a ction involves cell cycle regulation and apoptosis induction. Molecular docking studies revealed that compound 5k interacts with key EGFR residues through hydrogen bonding and cation – π interactions, highlighting its potential as an EGFR - targeted anticancer agent. These findings suggest that quinazolinone derivatives, especially 5k, are promising candidates for further development as anticancer therapeutics.