Chromone-3-aldehyde derivatives - sirtuin 2 inhibitors for correction of muscular dysfunction

The aim of the study was to evaluate experimentally, the myoprotective effect of new chromone-3-aldehyde derivatives in conditions of muscular dysfunction and to establish a potential mechanism of myoprotective activity - the blockade of the function of sirutin 2. Materials and methods. The effect of new chromone-3-aldehyde derivatives on the development of muscular dysfunction under the conditions of an electromiostimulation test, was studied. The degree of muscle fatigue was evaluated in the "grip-strength" and through test biochemical assays (determination of the activity of lactate dehydrogenase, creatine kinase, concentration of lactic and pyruvic acids, creatinine, myoglobin, and total protein) to determine the possible mechanism of action of the test compounds (5 new derivatives of chromone-3-aldehyde) and their effect on the function of sirtuin 2 was evaluated. Results. The study showed that chromone-3-aldehyde derivatives have a pronounced myoprotective effect associated with low toxicity (class 5 toxicity according to the GHS classification), which was confirmed by the results of the "grip-strength" test and biochemical tests data. Test compounds under the X3AC1, X3AOAC and X3AN codes evince sirtuin 2 inhibitory activity, which was reflected in a decrease in its concentration by 63.6% (p < 0.05); 130.2% (p < 0.05) and 218.8% (p < 0.05). Conclusion. The study showed that chromone-3-aldehyde derivatives are promising subjects for further study with the goal of creating a drug with a high myoprotective effect and an optimal safety profile.