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| Home > Articles > Published articles > Photoswitchable COX-2-Selective Inhibitors as Light-Regulated Anti-Inflammatory Agents |
| Home > Articles > Published articles > Photoswitchable COX-2-Selective Inhibitors as Light-Regulated Anti-Inflammatory Agents |
(Universitat Autònoma de Barcelona. Departament de Química) (Universitat Autònoma de Barcelona. Departament de Química) (Universitat Autònoma de Barcelona. Departament de Química) (Institut de Bioenginyeria de Catalunya) (Università degli Studi di Milano. Dipartimento di Scienze Farmaceutiche) (Universitat Autònoma de Barcelona. Departament de Química) (Universitat Autònoma de Barcelona. Departament de Química) (Universitat Autònoma de Barcelona. Departament de Química)
| Imprint: | American Chemical Society, 2026 |
| Abstract: | Despite their extensive use, the therapeutic potential of nonsteroidal anti-inflammatory drugs (NSAIDs) remains significantly constrained by adverse side effects. This limitation primarily arises from insufficient selectivity, as current NSAIDs inhibit not only the inducible cyclooxygenase-2 (COX-2) isoform at sites of inflammation but also constitutive COX-2 in healthy tissues and, frequently, cyclooxygenase-1. To address this challenge, we developed photoswitchable NSAIDs that combine COX-2 selectivity with light-controlled activity to enable spatiotemporal confinement of the therapeutic effect at inflamed tissues. Following computational design and screening of a library of azoaromatic derivatives of celecoxib─the most widely used COX-2 selective NSAID─three photoswitchable analogues were synthesized, which exhibited reversible and efficient trans-cis photoconversion. Light-controlled and selective COX-2 inhibition was demonstrated for these compounds in vitro, reaching up to 5-fold potency enhancement in macrophage assays upon photoisomerization from the initial, dark-adapted trans isomer to the cis state. The best candidate displayed in vivo efficacy in a zebrafish model of acute inflammation, where administration of the photoinduced cis form reduced leukocyte recruitment at the wound site. These findings position photoswitchable NSAIDs as a promising alternative to conventional drugs for treating inflammation and related conditions, including cancer. |
| Grants: | Agencia Estatal de Investigación PID2019-111493RB-I00 Agencia Estatal de Investigación PID2022-142609OB-I00 Agencia Estatal de Investigación PID2023-147140NB-I00 Agencia Estatal de Investigación PID2022-139826OB-I00 Generalitat de Catalunya 2021/SGR-00064 Generalitat de Catalunya 2021/SGR-01410 European Commission 945539 European Commission 101016787 European Commission 101130883 |
| Note: | Altres ajuts: acords transformatius de la UAB |
| Note: | Altres ajuts: CERCA Programme/Generalitat de Catalunya |
| Rights: | Aquest document està subjecte a una llicència d'ús Creative Commons. Es permet la reproducció total o parcial, la distribució, la comunicació pública de l'obra i la creació d'obres derivades, fins i tot amb finalitats comercials, sempre i quan es reconegui l'autoria de l'obra original.  |
| Language: | Anglès |
| Document: | Article ; recerca ; Versió publicada |
| Published in: | Journal of the American Chemical Society, Vol. 148, Num. 18 (May 2026) , p. 19226-19237, ISSN 1520-5126 |
