Small molecule inhibitors of HG-induced VEC ferroptosis: synthetic advances and therapeutic applications

Ferroptosis is a form of Regulated Cell Death (RCD) found in recent years. Its typical characteristics are the abnormal accumulation of intracellular iron ions and the accumulation of lipid peroxidation products. Since its first systematic elucidation in 2012, a large number of studies have shown that ferroptosis is involved in a variety of pathophysiological processes. It has been reported that the pathological process of diabetic cardiovascular diseases (DVD) is closely associated with the activation of ferroptosis. Due to the long-term hyperglycemic environment in diabetic patients, vascular endothelial cells (VECs) are susceptible to ferroptosis, ultimately contributing to vascular dysfunction. Therefore, the development of inhibitors targeting ferroptosis is of great significance for the prevention and treatment of diabetic vascular complications. This review systematically expounds the latest research progress of the molecular mechanism of ferroptosis, and discusses its role in DVD. In addition, this review also comprehensively summarizes the latest advances in the synthesis and application of drugs and specific inhibitors targeting the ferroptosis pathway for disease treatment, thereby providing new therapeutic strategies for DVD.