Quinoline-derived Anticancer Agents for Breast Cancer Therapy: Molecular Targets, Structure-activity Relationships, and Clinical Perspectives

Abstract:

Breast cancer remains one of the leading causes of cancer-related mortality among women worldwide, which highlights the need for more effective and safer therapeutic strategies. Quinoline is an important nitrogen-containing heterocycle that has been widely studied for the development of anticancer agents. Its structural flexibility facilitates extensive chemical manipulation, enabling alterations for potency, selectivity, physicochemical characteristics, and target interactions. Recent research has revealed how structural changes in quinoline derivatives affect their anticancer properties and interactions with biological targets for breast cancer treatment. Selected quinoline derivatives have shown biological activity involving ERα, EGFR, HER2, or VEGFR-2, but the exact role played by these target molecules in achieving these biological activities requires further confirmation for individual compounds. According to the literature, substituents such as halogens and electron donors can affect interactions with targets, inhibitory activities on kinases, physicochemical characteristics, and antiproliferative activity. This depends on the chemical series and experimental conditions. Several quinoline-containing or quinoline-derived drugs have clinical applications in oncology, including camptothecin, lenvatinib, neratinib, bosutinib, and cabozantinib. These findings underscore the significance of quinoline as an important framework in medicinal chemistry that continues to be explored for anti-cancer drugs. Among the selected papers, structural differences correlated with variations in target affinity, kinase inhibition, antiproliferative activity in cells, and selectivity; yet the SAR trends were series-specific, model-dependent, and assaydependent. Overall, the available evidence supports the potential of quinoline derivatives as promising leads for breast cancer drug discovery, although additional validation is needed for the targets, pharmacokinetics, safety, and clinical research. These findings provide useful guidance for future medicinal chemistry optimization.