Synthesis and Biological Evaluation of Arctigenin-Dipeptide Derivatives as Potential Anti-Fatigue Agents

Fatigue is a physiological phenomenon experienced by the human body when it undergoes prolonged physical and mental exertion, which can have detrimental effects on both health and work productivity. Previous research has demonstrated that arctigenin (ArcG) has the ability to enhance the physical performance of mice during exercise. In this study, five ArcG derivatives containing different dipeptides coupled via an ethoxy linker were synthesized and tested for their activities to improve exercise performance in mice. All of the derivatives extended the exhaustion distance of mice in the running wheel test. Derivative Z-B-4 exhibited the highest activity, showing that the mice ran a distance 1.3-fold greater than that of the ArcG group and 3.4-fold greater than that of the sport control group. Furthermore, Z-B-4 was found to increase the concentrations of superoxide dismutase (SOD) and catalase (CAT), while simultaneously decreasing levels of lactic acid (LA) and blood urea nitrogen (BUN) during exercise. This study provides new references and promising lead compounds for the development of antifatigue agents.