Study of the impact of newly synthesized chemical compounds with antihypoxic activity on life expectancy under hypoxia conditions (on the example of xanthine derivatives)

Abstract

A decrease in the supply of oxygen to the tissues leads to a change in the lipid layer of molecules and membrane enzymes. At the same time, the barrier, receptor, and catalytic functions of biological membranes are disrupted. The main causes of this pathological condition are energy deficit and activation of lipid peroxidation. The breakdown of phospholipids and inhibition of their synthesis lead to an increase in the concentration of unsaturated fatty acids and an increase in their peroxidation. Along with the therapeutic effect, antihypoxants can show side reactions: dyspeptic phenomena (nausea, vomiting, abdominal pain), cause headache, insomnia, palpitations, allergic reactions. Therefore, the search for more active and less toxic antihypoxants for the correction of oxygen deficiency is rational and expedient. The aim of this study was to study the antihypoxic activity of the first synthesized derivatives of ammonium salts of 3-methyl-7-methoxyethylxanthine-8-thioacetate in experiments on laboratory animals. The study of the antihypoxic activity of the synthesized substances was carried out on the model of acute normobaric hypoxia with hypercapnia in experiments on white Wistar rats. The article presents the data of an experimental study of the antihypoxic activity of 10 synthesized ammonium salts of 3-methyl-7-methoxy-ethylxanthine-8-thioacetate. It was established that most of the studied substances increased the lifespan of rats placed in sealed chambers under conditions of acute normobaric hypoxia. The drug for comparison, aminalon, also showed antihypoxic activity: it increased the lifespan of rats by 55.8%. Among the ammonium salts of 3-methyl-7-methoxyethylxanthine-8-thioacetate, the compound 4-ammonium salt of 3-methyl-7-methoxyethylxanthine-8-thioacetate pyrrolidinium (compound code g-7842) showed the greatest antihypoxic activity, which in a dose of 6.1 mg /kg increased the lifespan of rats in conditions of acute normobaric hypoxia by 74.6% (p<0.01). Based on the obtained data, it can be assumed that this compound has the ability to regulate biotransformation processes by changing the energy flows in the respiratory chain of mitochondria, and leads to a significant decrease in ATP consumption while simultaneously increasing the rate of oxidation of the ammonium salt of pyrrolidinium 7-methoxyethylxanthinyl-8-thioacetate. This helps to improve cell function and increase the lifespan of rats in conditions of acute normobaric hypoxia with hypercapnia. The data obtained from the study of the antihypoxic activity of the ammonium salts of 3-methyl-7-methoxyethylxanthinyl-8-thioacetate are the basis for a more in-depth study of the mechanisms of antihypoxic activity with the aim of creating a new effective drug with antihypoxic activity.