Chemoreactomic analysis of the antioxidant properties of vitamin B12 derivatives

Abstract

Background. Synthetic derivatives of vitamin B12 exhibit various physical, chemical and pharmacological properties. The development of methods for predicting the properties of these molecules based on their chemical structure is important for the targeted organic synthesis of corrins with the desired properties and range of applications in pharmacology.Objective: chemoreactomic assessment of the antioxidant effects of vitamin B12 and its derivatives: aquacobalamin, diaquacobinamide, aquacyano-forms of heptaethanolamine-, heptaethylenediamine-, heptamethyl- and heptabutylcobyrinates.Material and methods. The study was conducted using the method of chemoreactomic analysis, implemented within the framework of the algebraic theory of recognition and topological data analysis and based on the theory of isomorphism of labeled graphs and modern methods for predicting numerical target variables. To carry out chemoinformatic chemoreactome analysis, a special problem-oriented theory was developed within the boundaries of the combinatorial theory of solvability and the antioxidant properties of vitamin B12 derivatives were assessed (140 activities in total).Results. Significant differences were found in the properties of the studied substances in relation to oxidative stress. In test systems based on the oxidant 1,1-diphenyl-2-picrylhydrazyl, at different exposure times to molecules (15–60 min) in different concentrations (10–125 μM, 50–3000 μg/ml), aquacobalamin exhibited the most pronounced antioxidant properties at lower concentrations (up to 100 µM). At higher concentrations of substances (125 μM), the antioxidant activity of other vitamin B12 derivatives was higher. All studied molecules had a moderate antimicronutrient effect (total score of about 3.0; for most synthetic drugs, this score is higher than 3.6). Aquacobalamin was characterized by еhe least pronounced antimicronutrient effect (total score less than 0.8), which indicates an almost complete absence of antivitamin and antimineral action, corresponding to an average increase in the risk of a particular micronutrient excretion by no more than 5%.Conclusion. All the studied compounds exert antioxidant properties to one degree or another. Regardless of the choice of simulated test systems for assessing oxidative stress, aquacobalamin demonstrated antioxidant effects to the greatest extent and practically did not stimulate the loss of other micronutrients.