Synergistic aspirin derivatives treat hypoxic injury of coronary heart diseases
This study focuses on the microenvironment acidification caused by metabolic abnormalities and ion balance disturbances during cardiac ischemia,which can significantly trigger drug resistance and thus limit the therapeutic effect of coronary heart disease.To address this issue,we delve into the potential role of carbonic anhydrase inhibitors in enhancing drug efficacy through pH regulation.First,we evaluated the potential of the carbonic anhydrase inhibitor acetazolamide,in combination with aspirin,in alleviating myocardial hypoxic injury in a cellular model.Through high-throughput screening techniques,we systematically analyzed the synergistic effect of this drug combination and determined the optimal ratio.Next,we modified the structure of aspirin using acetazolamide as the structural basis,aiming to create novel derivatives with stronger myocardial protective activity.Using in vitro and in vivo models of myocardial hypoxic injury,we evaluated the biological activity and therapeutic efficacy of these derived compounds in detail.Animal experiments were approved by the Animal Ethics Committee of Southeast University(Ethics No.20240109001).The results showed that the structurally modified aspirin derivatives exhibited significant synergistic effects in alleviating myocardial hypoxic injury.This study reveals the mechanism of action of carbonic anhydrase inhibitors in the treatment of coronary heart disease and provides experimental and theoretical evidence for the development of novel coronary heart disease treatment drugs,which has important guiding significance for drug design and coronary heart disease treatment strategies.
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