Design and synthesis of novel antioxidants derived from chalcones and their protective effects on cardiomyocytes by activating Nrf2/ HO-1 pathway

The development of an antioxidant with high efficiency and low toxicity is a potential method for the treatment of myocardial injury. In this study, a series of new chalcone spiroheterocyclic derivatives with reduced toxicity and improved activity were designed and synthesized. Several compounds with antioxidant protection were screened via an H2O2-induced oxidative stress injury model in H9c2 cells, and a quantitative evaluation of structure activity relationship (QSAR) model was established through random forest (RF) algorithm. Among them, the most active compounds C1f and C3a can protect against oxidative myocardial injury in a dosedependent manner and promote colony growth. Mechanism studies have shown that compound C3a can effectively eliminate the production of reactive oxygen species (ROS) in oxidative stress injury by activating the Nrf2/HO-1 antioxidant signaling pathway, thus exerting a strong protective effect on the growth of H9c2 cells. In conclusion, in this stuty, we identified a novel class of antioxidants as potential drugs for the treatment of myocardial oxidative damage.