Study of\nChalcogen Aspirin Derivatives with Carbonic\nAnhydrase Inhibitory Properties for Treating Inflammatory Pain

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