Design, synthesis and Molecular modeling study of certain EGFRinhibitors with a quinazolinone scaffold as anti-hepatocellular carcinoma and Radio-sensitizers.

A set of novel N-substituted-2-((4-oxo-3-phenyl-3,4-dihydroquinazolin-2-yl)thio)acetamide 3-16 were designed and synthesized from 2-mercapto-3-phenylquinazolinone 2. The targeted compounds were screened for their cytotoxic activity against the hepatocellular carcinoma cell line HepG-2. Compounds 8, 9, 10, and 11 with IC ₅₀ values of 1.11, 4.28, 5.70, and 4.69 µM, respectively, showed 5.7- to 28-fold higher activities than the positive control doxorubicin (IC ₅₀ 32.02 µM). Furthermore, compounds 8 and 9 were tested for EGFR inhibitory activity and demonstrated IC ₅₀ values of 73.23 and 58.26  µM, respectively, when compared to erlotinib's IC ₅₀ value of 9.79 µM. The most potent compounds, 8 and 9, were subjected to a single dose of 8 Gy of γ-radiation, and their cytotoxic efficacy was found to increase after irradiation, demonstrating the synergistic effect of γ-irradiation. Molecular docking was adopted for the most active compounds to confirm their mode of action.
Competing Interests: Declaration of Competing Interest The authors declare that they have no known competing financial interests or personal relationships that could have appeared to influence the work reported in this paper.
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