Quinoline‐Based Scaffolds in Anticancer Drug Discovery: Molecular Targets, Synthetic Strategies, and Biological Advances

Cancer remains a major global health challenge, and the limited efficacy, systemic toxicity, multidrug resistance, and tumor recurrence associated with current therapies continue to drive the development of novel targeted anticancer agents. Quinoline-based heterocyclic scaffolds have emerged as valuable structural frameworks in anticancer drug discovery owing to their structural diversity and ability to interact with multiple oncogenic targets. This review provides a target-oriented overview of quinoline-based anticancer agents reported between 2019 and 2025, covering quinoline, quinazoline, quinoxaline, and a few selected nonquinoline nitrogen-containing heterocyclic derivatives. Recent advances in quinoline-based derivatives targeting ER, CDK4/6, topoisomerase I/II, epidermal growth factor receptor, PLCγ1, PI3K/AKT, and VEGFR-2/P-glycoprotein pathways are discussed with respect to their synthetic strategies, in vitro anticancer assay, and structure-activity relationships (SAR). This review integrates comparative SAR trends across diverse quinoline-based scaffolds, highlighting the influence of scaffold planarity, ring fusion, substitution patterns, linker architecture, and metal complexation on anticancer activity. In addition, clinically approved quinoline-based anticancer drugs, representative patents, and future perspectives are summarized to emphasize the translational potential of these scaffolds. Collectively, this review provides a comprehensive overview of recent advances to guide the rational design of next-generation quinoline-based anticancer agents.