Prognosis, antioxidant activity in silico and synthesis of 2,6-di-tert-butyl-4-[2-(R)-3H-benzimidazol-1-yl]-phenol derivatives

As part of the study, a method was developed for the synthesis of new benzimidazole derivatives modified with a fragment of spatially hindered phenol. The key step in the synthesis was the condensation reaction of 2,6-di-tert-butyl-p-benzoquinonimine with a number of aromatic and aliphatic aldehydes, which made it possible to obtain the desired compounds - 2,6-di-tert-butyl-4-[2-(R)-3H-benzimidazol-1-yl]-phenols. Identification and confirmation of the structure of the synthesized substances were carried out using a set of physicochemical methods, including elemental analysis, IR and ¹H-NMR spectroscopy. Assessment of antioxidant properties in vitro showed that a number of the obtained compounds have pronounced activity, and some of them have shown higher efficiency compared to reference substances - ubiquinone and dibunol. Objective - purposeful synthesis of a number of 2,6-di-tert-butyl-4-[2(R)-3H-benzimidazol-1-yl]-phenol derivatives using an improved procedure and subsequent comprehensive assessment of their antioxidant potential. Materials and methods. Synthesis of hybrid structures based on benzimidazole and shielded phenol was carried out using a modified method based on classical organic synthesis approaches. Elucidation of structure and identity of all target compounds were performed using a complex of analytical methods including IR, NMR ¹H spectroscopy and elemental analysis. The antioxidant activity of the synthesized samples was studied in a model system based on corn oil rich in a complex of saturated and unsaturated fatty acids. Lipid peroxidation in this system was induced both physically (UV irradiation) and chemically using the Fenton system (H₂O₂/Fe²⁺) as a free radical producer. For comparative analysis under identical conditions, the antiradical activity of the reference compounds ubiquinone and butylated hydroxytoluene was studied. The latter is the active ingredient of the drug dibunol and is a classic example of shielded phenol. Results. Antioxidant properties were studied in vitro for synthesized benzimidazole derivatives modified by introduction of spatially hindered phenol fragment. The results indicate a significant antioxidant effect exceeding that of the reference compounds (ubiquinone and dibunol). A number of leading compounds with maximum activity have been identified. Conclusion. The promise of 2,6-di-tert-butyl-4-[2-(R)-3H-benzimidazol-1-yl] phenols is due to their pronounced antioxidant activity, which opens up opportunities for studying a number of pharmacological effects mediated by it.

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