Synthesis and antioxidant properties of some new 5-phenethyl-3-thio-1,2,4-triazoles

Novel derivatives of 4-R-5-phenethyl-4H-1,2,4-triazole-3-thiols were synthesized. The proposed approaches and developed synthetic protocols provided the possibility to design 4-R-5-phenethyl-4H-1,2,4-triazole-3-thiols and their derivatives have been shown. The antioxidant activity of the synthesized compounds was evaluated in vitro by the method of the non-enzymatic initiation of BOD with salts of iron (II). When compared with existing antioxidants, some of our compounds were found to be more potent.


Introduction
Antioxidants are chemical structures that prevent the oxidation of other chemicals. They protect key cell components by neutralizing the harmful effect of free radicals which are natural products of cell metabolism. Oxidative stress leads to serious cell damage which results in various human diseases such as Alzheimer's disease, Parkinson's disease, atherosclerosis, cancer, arthritis, neurodegenerative disorders, etc. The deficiency of antioxidants in food also leads to oxidative stress, which indicates a lack of antioxidant substances consumed by humans. Therefore, the search of substances that could not only prevent but also increase the resistance of the human body to active forms of oxygen or nitrogen and interfere with the processes of oxidative stress is an important task of medicine and pharmacy (Pruglo 2017).
Extensive research is going on around the world to discover novel molecules to fight various infections and diseases. The demand, therefore, is to synthesize new bio-active molecules that are more effective and have fewer or no side effects (Chand et al. 2018).
Global achievements of scientists are engaged in the 1,2,4-triazole system simulation, studying various properties of the heterocycle and the formation on its base prospective "structures" can create favorable conditions for further search of new molecules with unique properties (Bihdan et al. 2018).
The analysis of scientific literature data indicates that the creation of new drugs of synthetic origin is based on the chemical substance hetero-and alkyl-cyclic characters.2 Therefore, the introduction into the structure of 5-phenethyl-3-thio-1,2,4-triazole these radicals as substitutes are relevant, have got practical significance and requires further study (Shcherbyna 2019).

Materials and methods
Physical-chemical properties of the synthesized compounds have been investigated according to the methods described in the State Pharmacopeia of Ukraine (The State Pharmacopoeia of Ukraine 2001).
The melting point has been determined by capillary method (2.2.14). The elemental composition of compounds has been set with the help of elemental analyzer Elementar Vario ЕL cube (CHNS) (standard -Sulfonamide). 1H NMR spectra of obtained compounds has been set with the help of Varian Mercury 200 MHz), solvent -DMSO-d6, internal standard -Tetramethylsilane (TMS). Chromatography-mass spectrometry studies have been conducted on gas-liquid chromatograph Agilent 1260 Infinity HPLC equipped with a mass spectrometer Agilent 6120 (in electrospray ionization (ESI)) (Kazicyna 1979;Sajdov and Sverdlova 1980).

Antioxidant activity
The method of evaluation of AOA was used in the non-enzymatic initiation of BOD with salts of iron (II). The egg lipoprotein suspension (ELS) was used as the substrate. ELS was prepared by homogenizing egg yolk with phosphate buffer (pH = 7.4). To the suspension was added the test compounds at a concentration of 10-3 mol / l. The free radical oxidation reaction is initiated by the addition of FeSO 4 × 7H 2 O solution. The mixture was incubated for 60 min at 37 °C. The reaction was stopped with a 20% solution of trichloroacetic acid with trilon B. After centrifugation for 30 min. a solution of thiobarbituric acid (TBA) was added to the supernatant and boiled in a water bath for 60 minutes. The colored complex of TBA-active products (TBA-AP) is extracted with the addition of n-butanol. Spectrophotometry determines the concentration of TBK-AP. Antioxidant activity (in percent) is determined by the formula: where AOA -antioxidant activity, % E 0 -the optical density of the control solution; E 1 -the optical density of a solution containing the test compound (vitamin C)

Conclusions
A series of novel 4-R-5-phenethyl-4H-1,2,4-triazole-3thiols derivatives, possessing antioxidant activity, was prepared. We have shown that the proposed approaches and developed synthetic protocols provided the possibility to design 4-R-5-phenethyl-4H-1,2,4-triazole-3-thiols and their derivatives. The pharmacological screening allowed the identification of only one lead compound whose antioxidant activity exceeded that for ascorbic acid. Further optimization of the structure to improve their activities is currently in progress.