farmaecFARMAKOEKONOMIKA. Modern Pharmacoeconomics and PharmacoepidemiologyФАРМАКОЭКОНОМИКА. Современная фармакоэкономика и фармакоэпидемиология2070-49092070-4933IRBIS LLC10.17749/2070-4909/farmakoekonomika.2024.239farmaec-1014Research ArticleORIGINAL ARTICLESОРИГИНАЛЬНЫЕ ПУБЛИКАЦИИChemoreactomic analysis of the antioxidant properties of vitamin B12 derivativesХемореактомный анализ антиоксидантных свойств производных витамина В12https://orcid.org/0000-0002-2659-7998ТоршинИ. Ю.TorshinI. Yu.

Торшин Иван Юрьевич – к.ф-м.н., к.х.н., старший научный сотрудник

WoS ResearcherID: C-7683-2018;

Scopus Author ID: 7003300274

ул. Вавилова, д. 44, корп. 2, Москва 119334

Ivan Yu. Torshin – PhD (Phys. Math.), PhD (Chem.), Senior Researcher

WoS ResearcherID: C-7683-2018;

Scopus Author ID: 7003300274

44 corp. 2 Vavilov Str., Moscow 119334

https://orcid.org/0000-0002-7663-710XГромоваО. А.GromovaO. A.

Громова Ольга Алексеевна – д.м.н., профессор, ведущий научный сотрудник

WoS ResearcherID: J-4946-2017;

Scopus Author ID: 7003589812

ул. Вавилова, д. 44, корп. 2, Москва 119334

Olga A. Gromova – Dr. Med. Sc., Professor, Leading Researcher

WoS ResearcherID: J-4946-2017;

Scopus Author ID: 7003589812

44 corp. 2 Vavilov Str., Moscow 119334

unesco.gromova@gmail.comhttps://orcid.org/0000-0003-1541-9480МайороваЛ. А.MaiorovaL. A.

Майорова Лариса Александровна – д.ф.-м.н., ведущий научный сотрудник

WoS ResearcherID: B-6288-2016;

Scopus Author ID: 58079684100

ул. Вавилова, д. 44, корп. 2, Москва 119334; пр. Шереметевский, д. 7, Иваново 153000

Larissa A. Maiorova – Dr. Phys. Math. Sc., Professor, Leading Researcher

WoS ResearcherID: B-6288-2016;

Scopus Author ID: 58079684100

44 corp. 2 Vavilov Str., Moscow 119334; 7 Sheremetyevsky Ave., Ivanovo 153000

Федеральный исследовательский центр «Информатика и управление» Российской академии наукРоссияFederal Research Center “Computer Science and Control”, Russian Academy of SciencesRussian FederationФедеральный исследовательский центр «Информатика и управление» Российской академии наук; Федеральное государственное бюджетное образовательное учреждение высшего образования «Ивановский государственный химико-технологический университет»РоссияFederal Research Center “Computer Science and Control”, Russian Academy of Sciences; Ivanovo State University of Chemistry and TechnologyRussian Federation202420052024173358367Copyright © Torshin I.Y., Gromova O.A., Maiorova L.A., 20242024Торшин И.Ю., Громова О.А., Майорова Л.А.Torshin I.Y., Gromova O.A., Maiorova L.A.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmacoeconomics.ru/jour/article/view/1014Background

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

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

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

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 the 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

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.

Актуальность

Актуальность. Синтетические производные витамина В12 проявляют различные физические, химические и фармакологические свойства. Разработка методов прогнозирования свойств этих молекул по их химической структуре важна для направленного органического синтеза корринов с желаемыми свойствами и спектром применения в фармакологии.

Цель

Цель: хемореактомная оценка антиоксидантных эффектов витамина В12 и его производных: аквакобаламин, диаквакобинамид, аквациано-формы гептаэтаноламин-, гептаэтилендиамин-, гептаметил- и гептабутилкобиринатов.

Материал и методы

Материал и методы. Исследование проведено с помощью метода хемореактомного анализа, реализованного в рамках алгебраической теории распознавания и топологического анализа данных и основанного на теории изоморфизма размеченных графов и современных методах прогнозирования числовых таргетных переменных. Для осуществления хемоинформационного хемореактомного анализа разработана специальная проблемно-ориентированная теория в границах комбинаторной теории разрешимости и проведены оценки антиоксидантных свойств производных витамина В12 (всего 140 активностей).

Результаты

Результаты. Найдены достоверные различия в свойствах исследованных веществ по отношению к оксидативному стрессу. В тест-системах, основанных на оксиданте 1,1-дифенил-2-пикрилгидразил, при различном времени воздействия молекул (15–60 мин) в различных концентрациях (10–125 мкМ, 50–3000 мкг/мл) аквакобаламин проявлял наиболее выраженные антиоксидантные свойства при более низких концентрациях (до 100 мкМ). При более высоких концентрациях веществ (125 мкМ) антиоксидантная активность других производных витамина В12 была выше. Все исследованные молекулы отличались умеренным антимикронутриентным действием (суммарный балл около 3,0; для большинства синтетических лекарств значение этого балла выше 3,6). Наименее выраженным антимикронутриентным действием характеризовался аквакобаламин (суммарный балл менее 0,8), что указывает на практически полное отсутствие антивитаминного и антиминерального действия – соответствует в среднем увеличению риска выведения того или иного микронутриента не более чем на 5%.

Заключение

Заключение. Все исследованные соединения в той или иной мере проявляют антиоксидантные свойства. Вне зависимости от выбора моделируемых тест-систем для оценки оксидативного стресса, аквакобаламин демонстрирует антиоксидантные эффекты в наибольшей степени и практически не стимулирует потерь других микронутриентов.

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The authors declare that there are no conflicts of interest present.