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.