Coumarin derivatives in pharmaceutical and biomedical engineering: Advances in design, synthesis, and therapeutic applications

Background: Coumarin derivatives have emerged as pivotal compounds in pharmaceutical and biomedical research due to their multifaceted therapeutic potential. Naturally occurring in a wide range of plants, coumarins exhibit diverse biological activities including antimicrobial, anticancer, antioxidant, anti-inflammatory, and anticoagulant effects. Their structural versatility, comprising fused benzene and α-pyrone rings, offers a valuable scaffold for the design of novel pharmacophores targeting complex diseases such as cancer, neurodegenerative disorders, and infectious diseases. Methods: This review synthesizes recent advancements in the design, synthesis, and therapeutic applications of coumarin derivatives. It explores traditional synthetic routes such as the Pechmann and Perkin condensations alongside modern environmentally friendly techniques including microwave-assisted synthesis and solvent-free reactions. Furthermore, the article examines mechanistic insights into coumarins' bioactivity, involving pathways like apoptosis induction, oxidative stress modulation, and inhibition of molecular targets including carbonic anhydrases, kinases, and efflux pumps. Results: Numerous coumarin derivatives have demonstrated significant in vitro and in vivo bioactivity. Antimicrobial derivatives showed broad-spectrum efficacy, including multidrug-resistant pathogens. Anticancer coumarins exhibited cytotoxicity in several human cancer cell lines, with some outperforming standard chemotherapeutics. Derivatives also showed potent antioxidant effects, primarily through radical scavenging and modulation of redox signaling pathways. On the other hand, the synthesis of hybrid coumarin molecules further enhanced biological efficacy and solubility, addressing key pharmacokinetic challenges. Conclusion: Coumarins represent a versatile and promising class of compounds for future drug development. Ongoing innovation in green chemistry and molecular design is essential to overcome existing limitations such as low aqueous solubility and regulatory restrictions. This review reinforces coumarins' potential as lead structures in pharmaceutical engineering, advocating for continued exploration of their applications across therapeutic domains.