Synthesis and evaluation of the antioxidant activity of {[1-aryl-4-chloro-1H-imidazole-5-YL) methyl]thio}alkane carboxylic acids

A. M. Grozav, A. O. Palamar, V. O. Chornous, I. M. Yaremiy, M. V. Vovk

Abstract


This study is devoted to development of the optimal conditions for synthesis and the study of some “structure – antioxidant activity” regularities of [(1-arylimidazole-5-yl)methylthio]alkane carboxylic acids, which structural analogues have found an application as medicinal products with a wide range of biological activities. The methodology of interaction between 4-cloro-5-chloromethylimidazoles with thioglycolic and thiopropionic acids has been used to obtain these compounds. Selection of the optimal reaction conditions has allowed to obtain target compounds in a dry dimethylformamide in the presence of potash at 50°C with yields of 75-82%. The compounds synthesized are high-melting crystalline substances that dissolve well in polar organic solvents and aqueous alkaline solutions. Their composition and structure have been confirmed by the results of elemental analysis and measurement data of IR-, 1H NMR- and chromatography mass-spectra. The study of the compounds synthesized has been conducted in vitro on biological samples. The antioxidant activity has been determined by the inhibition value of the ascorbate-dependent endogenous lipid peroxidation rate in rats’ liver found by the concentration of one of the products of free-radical lipid oxidation processes – malonaldehyde in the test sample. The results of the biological activity screening of the compounds synthesized show that all imidazole derivatives studied in the final concentration ranges of 10-3-10-1 M exhibit a high antioxidant action in the system in vitro. It has been found that the value of the antioxidant activity is influenced by the nature and position of the substituent in position 1 of imidazole. In particular, the presence of electron-acceptor substituents in the aryl fragment decreases the molecule activity in comparison with electron-donor substituents, wherein increase of the methylene groups quantity in the carboxyalkylthiol fragment does not significantly impact the antioxidant effect of the compounds.


Keywords


synthesis; imidazole; [(1-aryl-5-formyl-1H-imidazol-4-yl)thio]acetic acids; {[1-aryl-4-chloro-1H-imidazole-5-yl)methyl]thio}alkanecarboxylic acids; antioxidant activity

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DOI: https://doi.org/10.24959/88941

Abbreviated key title: Vìsn. farm.

ISSN 2415-8844 (Online), ISSN 1562-7241 (Print)