{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T02:29:15Z","timestamp":1791599355705,"version":"4.3.4"},"reference-count":64,"publisher":"MDPI AG","issue":"3","license":[{"start":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T00:00:00Z","timestamp":1773100800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"Fonds de Recherche du Qu\u00e9bec-Sant\u00e9","award":["doi.org\/10.69777\/342994"],"award-info":[{"award-number":["doi.org\/10.69777\/342994"]}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceutics"],"abstract":"<jats:p>Coumarin-based compounds are recognized for their chemical versatility and diverse biological activities, yet clinical applications remain largely confined to 4-hydroxycoumarin anticoagulants. To bridge this translational gap, coumarin scaffolds have been increasingly employed in prodrug design to enable controlled activation, targeted delivery, and theranostic functionality. This review critically evaluates whether coumarin-based prodrugs fulfill their therapeutic promise or remain primarily preclinical tools across oncology, inflammation, infectious diseases, and cardiovascular disorders. Strategies including enzymatic-, pH-, redox-, and light-triggered activation, as well as subcellular targeting and multifunctional hybrids, are discussed. Preclinical studies demonstrate improved bioavailability, reduced off-target toxicity, and real-time fluorescence monitoring, yet most compounds remain at the in vitro or small-animal model stage. Despite their mechanistic and conceptual potential, clinical translation is constrained by molecular complexity, pharmacokinetics, safety, and regulatory challenges. Overall, coumarins constitute a versatile multifunctional platform whose therapeutic impact relies on rigorous in vivo validation and strategic optimization.<\/jats:p>","DOI":"10.3390\/pharmaceutics18030341","type":"journal-article","created":{"date-parts":[[2026,3,10]],"date-time":"2026-03-10T12:39:08Z","timestamp":1773146348000},"page":"341","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":8,"title":["Coumarin-Based Prodrugs: Therapeutic Promise or Still Confined to Preclinical Exploration?"],"prefix":"10.3390","volume":"18","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-5514-7144","authenticated-orcid":false,"given":"Atziri Corin","family":"Chavez Alvarez","sequence":"first","affiliation":[{"name":"UMR-1240 Inserm, Universit\u00e9 Clermont Auvergne, 58 Rue Montalembert, 63005 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8004-5019","authenticated-orcid":false,"given":"Emmanuel","family":"Moreau","sequence":"additional","affiliation":[{"name":"UMR-1240 Inserm, Universit\u00e9 Clermont Auvergne, 58 Rue Montalembert, 63005 Clermont-Ferrand, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2026,3,10]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","unstructured":"Mustafa, Y.F. 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