Hydroxycoumarins and coumarin-based derivatives as kinase-targeted anticancer agents: Chemistry, structure-activity relationships, and mechanistic insights.

Protein kinases continue to be the primary therapeutic targets in cancer therapy because they mediate proliferation, survival, angiogenesis, metastasis, and resistance to treatment. Among these scaffolds, coumarins and hydroxycoumarins have emerged as highly versatile platforms for anticancer drug design due to their rigid benzopyran-2-one core, tunable substitution patterns, and potential for hybridization with kinase-privileged heterocycles. With an interest in medicinal chemistry, structure-activity relationships, and target binding and mechanisms, this review discusses the recently published primary literature on hydroxycoumarins and coumarin-derived derivatives developed as kinase-targeted anticancer agents. Existing evidence demonstrates that coumarin analogs have been considered against receptor tyrosine kinases (EGFR and VEGFR), survival-associated signaling nodes (PI3K/Akt/mTOR signaling), and cell cycle control kinases (CDKs and CK2). These subclasses exhibit various hydroxylation patterns and substitutions at key ring positions, linker architecture, heteroaryl fusion, and heteroaryl-aryl hybrid pharmacophores, each influencing ATP-pocket recognition, hinge-region interactions, and downstream biological responses, such as apoptosis, cell cycle arrest, and anti-migratory effects. Overall, coumarins have the potential to be used as a flexible scaffold family for the discovery of kinase-targeted anticancer drugs. However, further research is warranted to enhance the biochemical validation, optimize the selectivity, and facilitate the translational development of these compounds.