2. Academic Validation
  3. Study of Chalcogen Aspirin Derivatives with Carbonic Anhydrase Inhibitory Properties for Treating Inflammatory Pain

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

  • ACS Med Chem Lett. 2024 Aug 14;15(9):1559-1565. doi: 10.1021/acsmedchemlett.4c00284.
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
Affiliations

Affiliations

  • 1 Department of Neuroscience, Psychology, Drug Research and Child Health, Neurofarba, Pharmacology and Toxicology Section, University of Florence, 6-50139 Florence, Italy.
  • 2 Department of Clinical and Experimental Medicine, University of Pisa, 56126 Pisa, Italy.
  • 3 Department of Chemistry "Ugo Schiff" (DICUS), University of Florence, Via della Lastruccia 3-13, Sesto Fiorentino, I-50019 Florence, Italy.
  • 4 NEUROFARBA Department, Sezione di Scienze Farmaceutiche, University of Florence, Via Ugo Schiff 6, Sesto Fiorentino, 50019 Florence, Italy.
PMID: 39291024 DOI: 10.1021/acsmedchemlett.4c00284
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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