Cytotoxic, Genotoxic, Apoptotic, and Reactive Oxygen Generating Properties of Bioactive Quinoline Derivatives as Novel Anti Breast Cancer Agents.

The heterocyclic aromatic compound quinoline is widely used in pharmaceutical production due to its diverse biological activities, including anticancer properties. This study aimed to investigate the anticancer properties of newly synthesized quinoline derivatives: 5,7-dibromo-8-hydroxyquinoline (MC-5-2), 6,8-dibromotetrahydroquinoline (SO-3-3), nitroquinoline bromide (SO-22), and methoxyhydroxyquinoline bromide (SO-18) against breast cancer. Cytotoxic, genotoxic, apoptotic, and oxidative stress effects were assessed through ATP viability, comet, AO/EB staining, and H2DCF-DA assays using MCF-7 and MDA-MB-231 cancer cells and normal 184A1 breast epithelial cells. Intracellular glutathione levels were analyzed using the luminometric method using a GSH kit, and mitochondrial membrane potential through DiOC6(3) dye. ATP cell viability assay revealed significant reductions in cancer cell vitality with a lower impact on normal cells. MC-5-2 exhibited the highest cytotoxicity on MDA-MB-231 breast cancer cells, with the lowest IC value. Synthesized quinoline derivatives exhibited higher genotoxic and apoptotic effects through iROS-generating activity in a dose-dependent manner against breast cancer cells than the normal breast epithelial cells. Furthermore, quinoline derivatives disrupted mitochondrial membrane potential (ΔΨm) and reduced intracellular glutathione (GSH) levels, with MC-5-2 demonstrating the most substantial effects. These findings suggest that the newly synthesized quinoline derivatives, particularly MC-5-2, possess potent anticancer properties with a favorable selectivity profile.