Pharmacological screening of substances with cardioprotective effect in the group of 3-oxypyridine derivatives

Abstract

Introduction: The search for new compounds with antihypoxic and cardioprotective effects among 3-oxypyridine derivatives is promising. Research objectives: To study the anti-hypoxic and cardioprotective effects of 3-oxypyridine derivatives. Materials and methods: The search for compounds with an antihypoxic effect was carried out on blood leukocytes of rats in in vitro. To simulate hypoxia, Oil for Tissue Culture (SAGE) was used, 500 µl of which was applied into wells over a growth medium in order to block gas exchange. The cardioprotective effect of 3-oxypyridine derivatives was studied in the model of coronary-occlusive myocardial infarction (30 minutes of ischemia, 90 minutes of reperfusion). The level of troponin I (Tn I) was determined as a biochemical marker of myocardial damage. Results and discussion: In the in vitro experiments, when culting white blood cells, the lead compound in the group of 3-oxypyridine derivatives was identified under code LKhT 21–16, which increases the number of viable cells in the presence of hypoxia, surpassing the reference drugs. When confirming the chemical structure of the lead compound, LHT 21–16, a high sensitivity of the NMR spectroscopy method was revealed. In studying the cardioprotective activity in the model of coronary-occlusive myocardial infarction compound LHT 21–16 exerted a marked cardioprotective effect when reducing the size of the necrotic zone and the level of biochemical marker Tn I. Conclusions: 3-oxypiridine derivatives have antihypoxic and cardioprotective effects, which shows in a high number of surviving cells in the presence of hypoxia in the in vitro model, a reduced size of the necrotic zone and a reduced level of Tn I in the coronary-occlusive myocardial infarction.