| Summary: | In the design of antineoplastic drugs, quinazolinone derivatives are often used as small molecule inhibitors for kinases or receptor kinases, such as the EGFR tyrosine kinase inhibitor gefitinib, p38MAP kinase inhibitor <b>DQO-501</b>, and BRD4 protein inhibitor <b>PFI-1</b>. A novel and convenient approach for the solid-phase synthesis of dihydroquinazoline-2(1<i>H</i>)-one derivatives was proposed and 19 different compounds were synthesized. Cytotoxicity tests showed that most of the target compounds had anti-proliferative activity against HepG-2, A2780 and MDA-MB-231 cell lines. Among them, compounds <b>CA1-e</b> and <b>CA1-g</b> had the most potent effect on A2780 cells, with IC<sub>50</sub> values of 22.76 and 22.94 μM, respectively. In addition, in an antioxidant assay, the IC<sub>50</sub> of CA1-7 was 57.99 μM. According to bioinformatics prediction, ERBB2, SRC, TNF receptor, and AKT1 were predicted to be the key targets and play an essential role in cancer treatment. ADMET prediction suggested 14 of the 19 compounds had good pharmacological properties, i.e., these compounds displayed clinical potential. The correct structure of the final compounds was confirmed based on LC/MS, <sup>1</sup>H NMR, and <sup>13</sup>C NMR.
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