Antioxidant activity of salts of 2-(5-R-4-amino-1,2,4-triazole-3-ylthio)acetic acid

Abstract

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. The purpose of this work was to study the antioxidant activity (AOA) of salts of 2-(5-R-4-R-4H-1,2,4-triazole-3-ylthio)acetic acids with non-enzymatic initiation of free radical oxidation and to establish laws concerning chemical structure and biological effects of the studied substances. Materials and methods. Original derivatives of 1,2,4-triazole were used in the series of screening studies. The antioxidant activity of the compounds in vitro was determined according to the methodical recommendations of the State Pharmacological Center MoH Ukraine using the method of non-enzymatic initiation of lipid peroxide oxidation. Results. Dimethylammonium salt of 2-(4-amino-5-(2-bromophenyl)-1,2,4-triazole-3-ylthio)acetic acid (3c) possessed with a high AOA which reduced the content of TBK-AP by 54,95% ( р˂0,001). Derivatives of 4-amino-1,2,4-triazole had the most distinct AOA containing С5 carbon atoms 2-bromophenyl substituent. Thus, methylammonium salt 3b reduced the TBK-AP content by 80,31 (p˂0,001) which exceeds the reference ascorbic acid by 45,05% and the prototype thiotriazoline by 36,64%. Considering the data of experimental studies it was found that the most active substances among the studied substances were the initial 2-(4-amino-5-(2-bromophenyl)-1,2,4-triasole-3-ylthio)acetic acid (1b) which reduced TBK-AP level at 91,95% (p˂0,001) and its magnesium salt (3a) which suppressed the formation of this final product of LPO at 94,13% (p˂0,001). Some regularities of the chemical structure and AOA of the investigated substances were established after analyzing the data of experimental studies. Replacement of the morpholine cation in the morpholine molecule of 2-(4-amino-5-phenyl-1,2,4-triazole-3-ylthio)acetic acid (2d) on piperidine (2c) is accompanied by the appearance of AOA from 18,18% to 74,95%. Replacement of the same piperidine cation on the morpholine cation in the piperidine molecule of 2-(4-amino-5-(2-bromophenyl)-1,2,4-triazole-3-ylthio)acetic acid is accompanied by the expressive appearance of AOA, which is 90,27% (3f). Conclusions 8 compounds among the 12 which were studied were able to suppress the generation of free radicals in varying degrees of severity and possessed a distinct AOA. It was established that the introduction in the molecule of 2-(4-amino-5-phenyl-1,2,4-triazole-3-ylthio)acetic acid by С2 carbon atom of the phenyl nucleus of bromine atom was accompanied by an increase in the AOA of the studied substances.

Keywords

• 4-triazole
• antioxidant effect
• ascorbic acid
• thiobarbituric acid reactive substances (TBARs)