Coumarin as a Promising Scaffold in Drug Discovery: A Comprehensive Review of Synthetic Approaches, Structure–Activity Relationships, and Pharmacological Applications

Abstract:

Coumarins are an important class of oxygen-containing heterocyclic compounds that have attracted considerable attention in medicinal chemistry for their structural diversity, synthetic versatility, and broad spectrum of biological activities. Continued advances in synthetic methodologies and rational molecular design have expanded the therapeutic potential of coumarin derivatives, making an updated assessment of recent developments timely. This review critically examines recent progress in the synthesis, structure-activity relationships (SAR), and pharmacological properties of coumarin derivatives, with particular emphasis on emerging synthetic strategies, molecular hybridization, and their applications in drug discovery. Relevant literature was retrieved from Pub- Med, Scopus, ScienceDirect, ResearchGate, and Google Scholar, with a primary focus on studies published between 2016 and 2026, while landmark earlier reports were included to provide historical context. Recent developments in visible-light photocatalysis, green synthetic protocols, multicomponent reactions, C–H functionalization, and microwave-assisted synthesis have improved the efficiency and sustainability of coumarin preparation. SAR studies further demonstrate that the strategic incorporation of hydroxyl, methoxy, halogen, sulfonamide, Schiff base, and nitrogencontaining heterocyclic substituents enhances target affinity, selectivity, and pharmacokinetic behavior, yielding derivatives with antimicrobial, antioxidant, anti-inflammatory, anticancer, antiviral, antitubercular, and anti-Alzheimer's disease activities. Collectively, these advances provide valuable insights into the rational design of multifunctional coumarin-based therapeutics and identify promising directions for future medicinal chemistry research.