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 activity 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.