Synthesis and antioxidant activity of derivatives of 8Н -[1,2,4]triazolo[4,3-в][1,2,4]triazin-7-ones

Abstract

Oxidative stress is usually connected with many severe diseases, such as atherosclerosis, hypertension, Alzheimer’s disease etc. Therefore, the search for new antioxidants is a very important pharmacological task. The aim of the study – to synthesize new derivatives of 8-(41-hydroxy-3R-benzylidenamino)-6-tertbutyl-8Н-[1,2,4]triazolo[4,3-b][1,2,4]triazine-7-ones and to evaluate their antioxidant properties in screening test in vitro as compared with ionol and ascorbic acid. By interaction of equimolar amounts of 8-amino-6-tert-butyl-8H-[1,2,4]triazolo[4,3-b][1,2,4]triazin7-one with the corresponding aromatic and heterocyclic aldehydes in ethanol, a series of Schiff bases with the key fragment 8H-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-one were synthesized. The structure and purity of all the substances obtained were confirmed by 1H NMR spectroscopy. Screening of compound’s antioxidant activity (AOA) was studied in vitro by their ability to inhibit lipoperoxide formation, induced by FeSO4 in yolk lipoproteins emulsion. It is shown, that, depending on the structure, the test substances exhibit both antioxidant and prooxidant properties. The regularities of the chemical structure – pharmacological action are established. It is shown that the introduction of electron-withdrawing substituents (F, Cl, Br and COOMe) into the benzene ring leads to a decrease in the antioxidant properties as to the base molecule 6-tert-butyl-8(benzylideneamino)-8Н-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-оne 8 а without substitutes. The most active were derivatives of 8-(benzylideneamino)-6-~{tert}-butyl-[1,2,4]triazolo[4,3-b][1,2,4]triazin7-ones, which had a hydroxyl group and an additional oxyalkyl fragment in the third position of the benzene ring (8 l, 8 o). The data obtained substantiate the feasibility of further studying the most active derivatives of 6-tertbutyl-8-(benzylideneamino)-8Н-[1,2,4]triazolo[4,3-b][1,2,4]triazin-7-оnes as potential antioxidant agents.