Quinazolinone derivatives as new potential CDK4/6 inhibitors, apoptosis inducers and radiosensitizers for breast cancer

Background: Targeting CDK4/6 has advanced breast cancer treatment. Herein, new quinazolinones were synthesized with acetamide linkers as potential anti-breast cancer agents. Methods & results: In vitro cytotoxic evaluation on human breast cancer cell lines (MCF7 and MDA-MB-231) identified 1,3-benzodioxole (5d) to be of the highest potency. It showed good inhibitory activity on CDK4/6. Compound 5d arrested the cell cycle at the G1-phase, caused induction of early and late apoptosis in an Annexin V-FITC assay, led to an increase in the level of caspase-3 and upregulated Bax expression and downregulated Bcl-2 in MCF7 cells. Compound 5d showed good radiosensitizing activity when combined with a single dose of 8-Gy & gamma;-radiation. Conclusion: This study introduces quinazolinone scaffolds as new CDK4/6 inhibitors for breast cancer.

Automated summary

New quinazolinones with acetamide linkers were synthesized as potential anti-breast cancer agents. In vitro cytotoxic evaluation identified 1,3-benzodioxole (5d) as the most potent compound with good inhibitory activity on CDK4/6. Compound 5d arrested the cell cycle, induced apoptosis, and showed good radiosensitizing activity when combined with γ-radiation in breast cancer cells. This study introduces quinazolinone scaffolds as new CDK4/6 inhibitors for breast cancer treatment.