Novel 4-quinolone derivative inflicted cytotoxicity via intrinsic apoptotic pathway activation on human metastatic triple-negative breast cancer cells

Quinolones are a class of compounds that have shown promising potential as anticancer agents. However, the current quinolones in clinical trials are currently hampered by their efficacy issues. Therefore, we designed and synthesized novel 4-quinolone-3-carboxamide derivatives 14–67. All the synthesized compounds were initially screened for their cytotoxicity activity using the MTT assay method and evaluated for their anticancer activities against leukemia and breast cancer cells using the Differential Nuclear Staining (DNS) assay. Six screened compounds exhibited low CC₅₀ inhibitory effects against breast cancer cell lines, where compounds 24, 25, 52, and 65 also showed good activity (CC₅₀ = 6.99–11.17 μM) against the leukemia cell line (Jurkat). In vitro assessment showed that the most active compound, 65, exhibited significantly higher growth inhibition activity (CC₅₀ = 7.10–83.2 μM) in breast cancer cell lines, with less cytotoxicity observed in non-cancerous cells (MCF-10 A). The most active analog, compound 65, triggered apoptosis via membrane depolarization and caused cell cycle arrest at the S phase in the MDA-MB231/LM2-4 cell line. In conclusion, the outcomes indicate that compound 65 exhibits the potential to be a potent and effective anticancer agent, making it an excellent candidate for further research and development.