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. 2024 Aug 14;15(9):1559-1565.
doi: 10.1021/acsmedchemlett.4c00284. eCollection 2024 Sep 12.

Study of Chalcogen Aspirin Derivatives with Carbonic Anhydrase Inhibitory Properties for Treating Inflammatory Pain

Elena Lucarini  1 , Vanessa D'Antogiovanni  2 , Luca Antonioli  2 , Carla Ghelardini  1 , Lorenzo Di Cesare Mannelli  1 , Marta Ferraroni  3 , Maria Locuoco  3 , Antonella Capperucci  3 , Damiano Tanini  3 , Andrea Angeli  4 , Claudiu T Supuran  4
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Study of Chalcogen Aspirin Derivatives with Carbonic Anhydrase Inhibitory Properties for Treating Inflammatory Pain

Elena Lucarini et al. ACS Med Chem Lett. .

Erratum in

Abstract

Carbonic anhydrase (CA) inhibitors represent intriguing tools for treating pain. This study aims at studying the pharmacological profile of chalcogen bioisosteres of aspirin, as inhibitors of CA isoforms (hCA I, II, IV, VII, IX, and XII). Our results show that selenoaspirin (5) displayed markedly superior inhibitory potency across all tested isoforms compared to thioaspirin (7) and aspirin, with a strong selectivity against the isoform CA IX. X-ray crystallography confirmed that both compounds bind effectively within the active site of hCA II, revealing unique structural characteristics compared to those of aspirin. In a preclinical model of inflammatory pain, compound 7 exhibited a longer lasting antihyperalgesic effect than aspirin, though with a lower potency. Conversely, compound 5 exhibited both lower potency and efficacy than aspirin in reducing pain, which entailed both adverse effects. Nevertheless, the therapeutic potential of chalcogen-based aspirin derivatives as novel CA inhibitors deserves to be further explored for clinical applications.

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Conflict of interest statement

The authors declare no competing financial interest.

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