Hybrids of carbonic anhydrase and cyclooxygenase inhibitors attenuate cardiac hypoxic inflammatory injuries

Cardiac inflammation is easily accompanied by hypoxia, while hypoxia-induced injury and microenvironmental variations limit the efficacy of common anti-inflammatory drugs. In order to effectively attenuate myocardial injury caused by hypoxic and inflammatory injury, we designed and synthesized a kind of anti-inflammatory compounds by coupling cyclooxygenase (COX) and carbonic anhydrase (CA) inhibitors, and evaluated the ac-tivity and their mechanism in vitro and in vivo. It was found that these compounds were structurally stable and had two enzymatic inhibition activities. By inhibiting the activity of overexpressed CA under hypoxia, the acidic microenvironment can be regulated to inhibit the hypoxic injury, in which the pH-dependent primary drug resistance can be overcome to improve the anti-inflammatory effect of the COX inhibitor. Consequently, this study provides a new strategy for the treatment of cardiac inflammation accompanied by hypoxia.

Automated summary

In order to effectively attenuate myocardial injury caused by hypoxic and inflammatory injury, researchers designed and synthesized a kind of anti-inflammatory compounds by coupling cyclooxygenase and carbonic anhydrase inhibitors. The compounds were found to be structurally stable and had two enzymatic inhibition activities. By inhibiting the overexpression of carbonic anhydrase under hypoxia, the compounds can regulate the acidic microenvironment to inhibit hypoxic injury and improve the anti-inflammatory effect of the cyclooxygenase inhibitor. This study provides a new strategy for the treatment of cardiac inflammation accompanied by hypoxia.