pmedpharmФармация и фармакологияPharmacy & Pharmacology2307-92662413-2241Pyatigorsk Medical and Pharmaceutical Institute - branch of Volgograd State Medical Univer10.19163/2307-9266-2021-9-5-367-376pmedpharm-937Research ArticleФАРМАЦЕВТИЧЕСКАЯ И ТОКСИКОЛОГИЧЕСКАЯ ХИМИЯPHARMACEUTICAL AND TOXICOLOGICAL CHEMISTRYСИНТЕЗ И АНТИОКСИДАНТНАЯ АКТИВНОСТЬ ПРОИЗВОДНЫХ (E)-3-(3-(4-ОКСО-4H-ХРОМЕН-3-ИЛ) АКРИЛОИЛ)-2H-ХРОМЕН-2-ОНАSYNTHESIS AND ANTIOXIDANT ACTIVITY OF (E)-3-(3-(4-OXO-4H-CHROMEN-3-YL)ACRYLOYL) 2H-CHROMEN-2-ONE DERIVATIVEShttps://orcid.org/0000-0001-7891-8338ШатохинС. С.ShatokhinS. S.

аспирант кафедры органической химии

post-graduate student of the Department of Organic Chemistry 

shatohin.stanislav95@yandex.ruhttps://orcid.org/0000-0001-7182-462XТускаевВ. А.TuskaevV. A.

кандидат фармацевтических наук, ведущий научный сотрудник химического факультета, ФГБОУ ВО «Московский государственный университет имени М.В. Ломоносова»; ведущий научный сотрудник ИНЭОС РАН

Candidate of Sciences (Pharmacy), Leading Researcher, Faculty of Chemistry, Lomonosov Moscow State University; Leading Researcher, Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences

tuskaev@yandex.ruhttps://orcid.org/0000-0003-4654-9974ГагиеваС. Ч.GagievaS. Ch.

кандидат химических наук, ведущий научный сотрудник химического факультета

Candidate of Sciences (Chemistry), Leading Researcher,

sgagieva@yandex.ruhttps://orcid.org/0000-0003-0889-7855ПоздняковД. И.PozdnyakovD. I.

кандидат фармацевтических наук, доцент кафедры фармакологии с курсом клинической фармакологии

Candidate of Sciences (Pharmacy), Associate Professor of the Department of Pharmacology with a course in Clinical Pharmacology 

pozdniackow.dmitry@yandex.ruhttps://orcid.org/0000-0002-2756-9382ОганесянЭ. Т.OganesyanE. T.

доктор фармацевтических наук, профессор, заведующий кафедрой органической химии

Doctor of Sciences (Pharmacy), Professor, Head of the Department of Organic Chemistry 

edwardov@mail.ruПятигорский медико-фармацевтический институт – филиал федерального государственного бюджетного образовательного учреждения высшего образования «Волгоградский государственный медицинский университет» Министерства здравоохранения Российской Федерации 357532, Россия, г. Пятигорск, пр-кт Калинина, 11РоссияPyatigorsk Medical and Pharmaceutical Institute – branch of Volgograd State Medical University, 11, Kalinin Ave., Pyatigorsk, Russia, 357532Russian Federation1. Федеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный университет имени М.В. Ломоносова» 119991, Россия, г. Москва, Ленинские горы, 1, стр. 3 2. Федеральное государственное бюджетное учреждение науки «Институт элементоорганических соединений имени А.Н. Несмеянова» Российской академии наук (ИНЭОС РАН) 119991, Россия, г. Москва, ул. Вавилова, 28Россия1. Lomonosov Moscow State University, Bldg. 3, 1, Leninskie Gory, Moscow, Russia, 119991 2. Nesmeyanov Institute of Organoelement Compounds of Russian Academy of Sciences, 28, Vavilov St., Moscow, Russia, 119991Russian FederationФедеральное государственное бюджетное образовательное учреждение высшего образования «Московский государственный университет имени М.В. Ломоносова» 119991, Россия, г. Москва, Ленинские горы, 1, стр. 3РоссияLomonosov Moscow State University, Bldg. 3, 1, Leninskie Gory, Moscow, Russia, 119991Russian Federation20212510202195367376Copyright © Шатохин С.С., Тускаев В.А., Гагиева С.Ч., Поздняков Д.И., Оганесян Э.Т., 20212021Шатохин С.С., Тускаев В.А., Гагиева С.Ч., Поздняков Д.И., Оганесян Э.Т.Shatokhin S.S., Tuskaev V.A., Gagieva S.C., Pozdnyakov D.I., Oganesyan E.T.Данная работа распространяется под лицензией Creative Commons Attribution 4.0.This work is licensed under a Creative Commons Attribution 4.0 License.https://www.pharmpharm.ru/jour/article/view/937Цель

Цель. На основе результатов прогноза in silico получить и охарактеризовать ряд производных (E)-3-(3-(4-оксо-4H-хромен-3-ил)акрилоил)-2H-хромен-2-она, а также изучить их антиоксидантную активность.

Материалы и методы

Материалы и методы. Синтез целевых соединений осуществляли конденсацией замещенных 3-формилхромонов и 3-ацетилкумаринов в условиях кислотного катализа. ЯМР1Н спектры регистрировали на приборе Bruker Avance-400 (400 МГц) и Bruker Avance-300 (300 МГц) в растворах в дейтерированном хлороформе (CDCl3) или дейтерированном диметилсульфоксиде (DMSO-d6). Масс-спектры (ESI) были получены на масс-спектрометре Finnigan LCQ Advantage (США). Температуры плавления соединений определяли на приборе ПТП (М). Квантово-химические расчеты проводили на основе теории функционала плотности с помощью программы Gaussian 09 методом B3LYP/6-311G (d,p), а также с помощью онлайн-сервиса Way2Drug PASS Online. Антирадикальная активность соединений изучена методом DPPH-теста, а хелатирующие свойства оценены о-фенантролиновым методом.

Результаты

Результаты. Получено и охарактеризовано 15 производных (E)-3-(3-(4-оксо-4H-хромен-3-ил)акрилоил)-2H-хромен-2-она. Расчеты на основе теории функционала плотности показали, что высшая занятая молекулярная орбиталь, проявляющая электронодонорные свойства, локализована на пропеноновом фрагменте, что подтверждает вероятность проявления антирадикальных свойств. По данным прогноза вероятного спектра биологической активности, полученные соединения с большей вероятностью могут проявлять прямую антиоксидантную активность. По результатам проведенного in vitro изучения антиоксидантной активности установлено, что соединения 1-15 проявляют наибольшую активность в отношение DPPH-радикала, что подтверждает полученные прогностические данные.

Заключение

Заключение. Таким образом, на основании данных in silico прогноза получено и охарактеризовано 15 производных (E)-3-(3-(4-оксо-4H-хромен-3-ил)акрилоил)-2H-хромен-2-она, для которых методом in vitro изучена антиоксидантная активность. Установлено, что соединения 1-15 в значительной степени проявляют антирадикальную активность.

The aim is based on the results of the in silico prediction, to obtain and characterize a number of (E)-3-(3-(4-oxo-4H-chromen-3-yl)acryloyl)-2H-chromen-2-one derivatives, and also to study their antioxidant activity.

Materials and methods

Materials and methods. The synthesis of the target compounds was carried out by condensation of substituted 3-formylchromones and 3-acetylcoumarins under the acid catalysis conditions. 1H NMR spectra were recorded on the instruments of Bruker Avance-400 (400 MHz) and Bruker Avance-300 (300 MHz) in the solutions of CDCl3 or DMSO-d6. Mass spectra (ESI) were obtained on a Finnigan LCQ Advantage mass spectrometer (USA). The melting points of the compounds were determined on a PTP (M) instrument. Quantum-chemical calculations were carried out on the basis of a density functional theory using the Gaussian 09 program using the B3LYP/6-311G (d, p) method, as well as using the Way2Drug (PASS Online) online service. The antiradical activity of the compounds was studied by the DPPH test, and the chelating properties were assessed by the o-phenanthroline method.

Results

Results. 15 derivatives of (E)-3-(3-(4-oxo-4H-chromen-3-yl)acryloyl)-2H-chromen-2-one have been obtained and characterized. The calculations based on the density functional theory showed that the highest occupied molecular orbital exhibiting electron-donating properties is localized on the propenone fragment, which confirms the likelihood of the manifestation of antiradical properties. According to the prediction of the probable spectrum of the biological activity, the obtained compounds are more likely to exhibit their direct antioxidant activity. According to the results of the in vitro study of the antioxidant activity, it was found out that compounds 1-15 are the most active in relation to the DPPH radical, which confirms the obtained prognostic data.

Conclusion

Conclusion. Thus, based on the in silico prediction data, 15 derivatives of (E)-3-(3-(4-oxo-4H-chromen-3-yl)acryloyl)-2H-chromen-2-one have been obtained and characterized, for which the method antioxidant activity has been studied in vitro. It was found out that compounds 1-15 exhibit the antiradical activity to a large extent.

3-формилхромон3-ацетилкумаринхалконыDFT расчетыантиоксидантная активность3-formylchromone3-acetylcoumarinchalconesDFT calculationsantioxidant activityДанное исследование не имело финансовой поддержки от сторонних организацийThis study did not have any funding from third-party organizations.ReferencesЧугунова Е.А., Газизов А.С., Бурилов А.Р., Юсупова Л.М., Пудовик М.А., Синяшин О.Г. Бензофуроксаны: синтез, свойства и биологическая активность // Известия Академии Наук: Серия химическая. – 2019. – Т. 11. – С. 887–910.Chugunova EA, Gazizov AS, Burilov AR, Yusupova LM, Pudovik MA, Sinyashin OG, Benzofuroxans: synthesis, properties and biological activity [Benzofuroksany: sintez, svojstva i biologicheskaya aktivnost’]. Bulletin of the Academy Sciences: Chemical series. 2019;11:887–910. RussianOlennikov D.N., Kashchenko N.I., Chirikova N.K. A Novel HPLC-Assisted Method for Investigation of the Fe2+-Chelating Activity of Flavonoids and Plant Extracts // Molecules. – 2014. – Vol. 19, No.11. – P. 18296–18316. DOI: 10.3390/molecules191118296.Olennikov DN, Kashchenko NI, Chirikova NK. A Novel HPLC-Assisted Method for Investigation of the Fe2+-Chelating Activity of Flavonoids and Plant Extracts. Molecules. 2014;19(11):18296–316. DOI: 10.3390/molecules191118296.Waris G., Ahsan H. Reactive oxygen species: Role in the development of cancer and various chronic conditions // J. Carcinog. – 2006. – Vol. 5. – P. 14–21. DOI: 10.1186/1477-3163-5-14.Waris G, Ahsan H. Reactive oxygen species: role in the development of cancer and various chronic conditions. J Carcinog. 2006 May 11;5:14. DOI: 10.1186/1477-3163-5-14.Valko M., Leibfritz D., Moncol J., Cronin M. T. D., Mazur M., Telser J. Free radicals and antioxidants in normal physiological functions and human disease // Int. J Biochem. Cell. Biol. – 2007. – Vol. 39, No.1. – P. 44–84. DOI: 10.1016/j.biocel.2006.07.001.Valko M, Leibfritz D, Moncol J, Cronin MT, Mazur M, Telser J. Free radicals and antioxidants in normal physiological functions and human disease. Int J Biochem Cell Biol. 2007;39(1):44–84. DOI: 10.1016/j.biocel.2006.07.001.Ahmad A., Kaleem M., Ahmed Z., Shafiq H. Therapeutic potential of flavonoids and their mechanism of action against microbial and viral infections-A review // Food Research International. – 2015. – Vol. 77. – P. 221–235. DOI: /10.1016/j.foodres.2015.06.021.Ahmad A, Kaleem M, Ahmed Z, Shafiq H. Therapeutic potential of flavonoids and their mechanism of action against microbial and viral infections-A review. Food Research International. 2015;77:221–35. DOI: /10.1016/j.foodres.2015.06.021.de Araújo F.F., de Paulo Farias D., Neri-Numa I.A., Pastore G.M. Polyphenols and their applications: An approach in food chemistry and innovation potential // Food Chemistry. – 2021. – Vol. 338. – 127535. DOI: 10.1016/j.foodchem.2020.127535.de Araújo FF, de Paulo Farias D, Neri-Numa IA, Pastore GM. Polyphenols and their applications: An approach in food chemistry and innovation potential. Food Chem. 2021 Feb 15;338:127535. DOI: 10.1016/j.foodchem.2020.127535.Шатохин С.С., Тускаев В.А., Гагиева С.Ч., Оганесян Э.Т. Синтез гетероциклических аналогов изофлавона и гомоизофлавона на основе 3-формилхромона // Известия Академии Наук: Серия химическая. – 2021. – Т. 6. – С. 1011–1045.Shatokhin SS, Tuskaev VA, Gagieva SCh, Oganesyan ET. Synthesis of heterocyclic analogs of isoflavone and homoisoflavone based on 3-formylchromone [Sintez geterociklicheskih analogov izoflavona i gomoizoflavona na osnove 3-formilhromona]. Bulletin of the Academy Sciences: Chemical series. 2021;6:1011–45. RussianLichota A., Gwozdzinski L., Gwozdzinski K. Therapeutic potential of natural compounds in inflammation and chronic venous insufficiency // Eur J Med Chem. – 2019. – Vol. 176. – P. 68–91. DOI: 10.1016/j.ejmech.2019.04.075.Lichota A, Gwozdzinski L, Gwozdzinski K. Therapeutic potential of natural compounds in inflammation and chronic venous insufficiency. Eur J Med Chem. 2019 Aug 15;176:68–91. DOI: 10.1016/j.ejmech.2019.04.075.Loh Y. C., Chan S.Y., Tew W.Y., Oo C.W., Yam M.F. New flavonoid-based compound synthesis strategy for antihypertensive drug development // Life Sciences. – 2020. – Vol. 249. – Art. No. 117512. DOI: 10.1016/j.lfs.2020.117512.Loh YC, Chan SY, Tew WY, Oo CW, Yam MF. New flavonoid-based compound synthesis strategy for antihypertensive drug development. Life Sci. 2020 May 15;249:117512. DOI: 10.1016/j.lfs.2020.117512.Perez-Vizcaino F., Fraga C. G. Research trends in flavonoids and health // Archives of Biochemistry and Biophysics. – 2018. – Vol. 646. – P. 107–112. DOI: 10.1016/j.abb.2018.03.022.Perez-Vizcaino F, Fraga CG. Research trends in flavonoids and health. Arch Biochem Biophys. 2018 May 15;646:107–12. DOI: 10.1016/j.abb.2018.03.022.Raffa D., Maggio B., Raimondi M.V., Plescia F., Dainone G. Recent discoveries of anticancer flavonoids // European Journal of Medicinal Chemistry. – 2017. – Vol. 142. – P. 213–228. DOI: 10.1016/j.ejmech.2017.07.034.Raffa D, Maggio B, Raimondi MV, Plescia F, Daidone G. Recent discoveries of anticancer flavonoids. Eur J Med Chem. 2017 Dec 15;142:213–228. DOI: 10.1016/j.ejmech.2017.07.034.Heim K.E., Tagliaferro A.R., Bobilya D.J. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships // Journal of Nutritional Biochemistry. – 2002. – Vol. 13, No.10. – P. 572–584. DOI: 10.1016/S0955-2863(02)00208-5.Heim KE, Tagliaferro AR, Bobilya DJ. Flavonoid antioxidants: chemistry, metabolism and structure-activity relationships. J Nutr Biochem. 2002 Oct;13(10):572–584. DOI: 10.1016/s0955-2863(02)00208-5.Mladěnka P., Zatloukalová L., Filipský T., Radomír Hrdina. Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity // Free Radical Biology & Medicine. – 2010. – Vol. 49, No.6. – P. 963–975. DOI: 10.1016/j.freeradbiomed.2010.06.010.Mladenka P, Zatloukalová L, Filipský T, Hrdina R. Cardiovascular effects of flavonoids are not caused only by direct antioxidant activity. Free Radic Biol Med. 2010 Sep 15;49(6):963–75. DOI: 10.1016/j.freeradbiomed.2010.06.010.Procházková D., Boušová I., Wilhelmová N. Antioxidant and prooxidant properties of flavonoids // Fitoterapia. – 2011. – Vol. 82. – P. 513–523. DOI: 10.1016/j.fitote.2011.01.018.Procházková D, Boušová I, Wilhelmová N. Antioxidant and prooxidant properties of flavonoids. Fitoterapia. 2011 Jun;82(4):513–23. DOI: 10.1016/j.fitote.2011.01.018.Agati G., Azzarello E., Pollastri S., Tattini M. Flavonoids as antioxidants in plants: Location and functional significance // Plant Science. – 2012. – Vol. 196. – P. 67–76. DOI: 10.1016/j.plantsci.2012.07.014.Agati G, Azzarello E, Pollastri S, Tattini M. Flavonoids as antioxidants in plants: location and functional significance. Plant Sci. 2012 Nov;196:67–76. DOI: 10.1016/j.plantsci.2012.07.014.Самет А.В., Сильянова Е.А., Ушкарев В.И., Семенова М.Н., Семенов В.В. Синтез 3,4-диарил- и 3-арил-4-ацилпирролов и изучение их антимитотической активности // Известия Академии Наук: Серия химическая. – 2018. – Т. 5. – С. 858–865.Samet AV, Silyanova EA, Ushkarev VI, Semenova MN, Semenov VV. Synthesis of 3,4-diaryl- and 3-aryl-4-acylpyrroles and study of their antimitotic activity [Sintez 3,4-diaril- i 3-aril-4-acilpirrolov i izuchenie ih antimitoticheskoj aktivnosti]. Bulletin of the Academy Sciences: Chemical series. 2018;5:858–65. RussianОсипова В.П., Половинкина М.А., Телекова Л.Р., Великородов А.В., Степкина Н.Н., Берберова Н.Т. Синтез и антиоксидантная активность новых гидроксипроизводных халконов // Известия Академии Наук: Серия химическая. – 2020. – Т. 5. – С. 504–509.Osipova VP, Polovinkina MA, Telekova LR, Velikorodov AV, Stepkina NN, Berberova NT. Synthesis and antioxidant activity of new hydroxy derivatives of chalcones [Sintez i antioksidantnaya aktivnost’ novyh gidroksiproizvodnyh halkonov]. Bulletin of the Academy Sciences: Chemical series. 2020; 5: 504-9. RussianFoti M.C. Use and Abuse of the DPPH• Radical // J. Agricult. Food Chem. – 2015. – Vol. 63, No.40. – P. 8765–8776.59. DOI: 10.1021/acs.jafc.5b03839.Foti MC. Use and Abuse of the DPPH(•) Radical. J Agric Food Chem. 2015 Oct 14;63(40):8765–76. DOI: 10.1021/acs.jafc.5b03839.Benzie I.F., Choi S.W. Antioxidants in food: Content, Measurement, Significance, Action, Cautions, Caveats, and Research Needs // Adv. Food Nutr. Res. – 2014. – Vol. 71. – P. 1–53. DOI: 10.1016/B978-0-12-800270-4.00001-8.Benzie IF, Choi SW. Antioxidants in food: content, measurement, significance, action, cautions, caveats, and research needs. Adv Food Nutr Res. 2014;71:1–53. DOI: 10.1016/B978-0-12-800270-4.00001-8.Soren S. Antioxidant Potential and Toxicity Study of the Cerium Oxide Nanoparticles Synthesized by Microwave-Mediated Synthesis // Appl. Biochem. Biotechnol. – 2015. – Vol. 177, No.1. – P. 148–161. DOI: 10.1007/s12010-015-1734-8.Soren S, Jena SR, Samanta L, Parhi P. Antioxidant Potential and Toxicity Study of the Cerium Oxide Nanoparticles Synthesized by Microwave-Mediated Synthesis. Appl Biochem Biotechnol. 2015 Sep;177(1):148–61. DOI: 10.1007/s12010-015-1734-8.Mansour E., Nassar E.M., El-Farargy A.F., Abdelrazek F.M. An Eco-Friendly Synthesis of Some Novel Chromene-Based Heterocyclic Compounds of Biological Interest // Russ. J. Bioorg. Chem. – 2020. – Vol. 46, No.4. – P. 582–589.Mansour E, Nassar EM, El-Farargy AF, Abdelrazek FM. An Eco-Friendly Synthesis of Some Novel Chromene-Based Heterocyclic Compounds of Biological Interest. Russ J Bioorg Chem. 2020; 46(4):582–9.Mourad A.K., Mohamed F.K., Essawy A.E.-N. I., Sayed S.M. A comprehensive synthesis and antimicrobial evaluation of some fused heterocycles based on coumarin moiety // Arkivoc. – 2018. – No.7. – P. 407–422. DOI: 10.24820/ark.5550190.p010.674.Mourad AK, Mohamed FK, Essawy AE-NI, Sayed SM. A comprehensive synthesis and antimicrobial evaluation of some fused heterocycles based on coumarin moiety. Arkivoc. 2018;7:407–22. DOI: 10.24820/ark.5550190.p010.674Siddiqui Z.N. A convenient synthesis of coumarinyl chalcones using HClO4–SiO2: A green approach // Arab. J. Chem. – 2019. – Vol. 12, No.8. – P. 2788–2797. DOI: 10.1016/J.ARABJC.2015.06.013.Siddiqui ZN. A convenient synthesis of coumarinyl chalcones using HClO4–SiO2: A green approach. Arab J Chem. 2019;12(8):2788–97. DOI: 10.1016/J.ARABJC.2015.06.013.Siddiqui Z.N., Musthafa T.N.M. An efficient and novel synthesis of chromonyl chalcones using recyclable Zn(l-proline)2 catalyst in water // Tetrahedron Lett. – 2011. – Vol. 52, No.31. – P. 4008–4013. DOI: 10.1016/j.tetlet.2011.05.118.Siddiqui ZN, Musthafa TNM. An efficient and novel synthesis of chromonyl chalcones using recyclable Zn(l-proline)2 catalyst in water. Tetrahedron Lett. 2011;52(31):4008–13. DOI: 10.1016/j.tetlet.2011.05.118.De Vleeschouwer F., Van Speybroeck V., Waroquier M., Geerlings P., De Proft F. Electrophilicity and nucleophilicity index for radicals // Org. Lett. – 2007. – Vol. 9, No.14. – P. 2720–2724. DOI: 10.1021/ol071038k.De Vleeschouwer F, Van Speybroeck V, Waroquier M, Geerlings P, De Proft F. Electrophilicity and nucleophilicity index for radicals. Org Lett. 2007 Jul 5;9(14):2721–4. DOI: 10.1021/ol071038k.Becke A.D. Density-functional exchange-energy approximation with correct asymptotic behavior // Phys. Rev. A. – 1988. – Vol. 38, No.6. – P. 3098–3100. DOI: 10.1103/PhysRevA.38.3098.Becke AD. Density-functional exchange-energy approximation with correct asymptotic behavior. Phys Rev A Gen Phys. 1988 Sep 15;38(6):3098–100. DOI: 10.1103/physreva.38.3098.Филимонов Д.А., Дружиловский Д.С., Лагунин А.А., Глориозова Т.А., Рудик А.В., Дмитриев А.В., Погодин П.В., Поройков В.В. Компьютерное прогнозирование спектров биологической активности химических соединений: возможности и ограничения // Biomedical Chemistry: Research and Methods. – 2018. – Т. 1, №1. – e00004. DOI: 10.18097/bmcrm00004.Filimonov DA, Druzhilovskiy DS, Lagunin AA, Gloriozova TA, Rudik AV, Dmitriev AV, Pogodin PV, Poroikov VV. Computer prediction of biological activity spectra of chemical compounds: possibilities and limitations. Biomedical Chemistry: Research and Methods. 2018; 1(1): e00004. DOI: 10.18097 / bmcrm00004.Sies H. Oxidative stress: a concept in redox biology and medicine // Redox Biol. – 2015. – Vol. 4. – P. 180–183. DOI: 10.1016/j.redox.2015.01.002.Sies H. Oxidative stress: a concept in redox biology and medicine. Redox Biol. 2015;4:180–3. DOI: 10.1016/j.redox.2015.01.002.Forrester S.J., Kikuchi D.S., Hernandes M.S., Xu Q., Griendling K.K. Reactive Oxygen Species in Metabolic and Inflammatory Signaling // Circ Res. – 2018. – Vol. 122, No.6. – P. 877–902. DOI: 10.1161/CIRCRESAHA.117.311401.Forrester SJ, Kikuchi DS, Hernandes MS, Xu Q, Griendling KK. Reactive Oxygen Species in Metabolic and Inflammatory Signaling. Circ Res. 2018 Mar 16;122(6):877–902. DOI: 10.1161/CIRCRESAHA.117.311401.Al-Shehri S.S. Reactive oxygen and nitrogen species and innate immune response // Biochimie. – 2021. – Vol. 181. – P. 52–64. DOI: 10.1016/j.biochi.2020.11.022.Al-Shehri SS. Reactive oxygen and nitrogen species and innate immune response. Biochimie. 2021 Feb;181:52–64. DOI: 10.1016/j.biochi.2020.11.022.Alkadi H. A Review on Free Radicals and Antioxidants. Infect Disord Drug Targets. 2020. – Vol. 20, No.1. – P. 16–26. DOI: 10.2174/1871526518666180628124323.Alkadi H. A Review on Free Radicals and Antioxidants. Infect Disord Drug Targets. 2020;20(1):16–26. DOI: 10.2174/1871526518666180628124323.González M., Tereschuk M.L., Criado S. The activity of propolis in the scavenging of vitamin B2-photogenerated ROS // Redox Rep. – 2015. – Vol. 20, No.6. – P. 246–253. DOI: 10.1179/1351000215Y.0000000033.González M, Tereschuk ML, Criado S, Reynoso E, Challier C, Agüero MB, Luna L, Ferrrari G, Montaña MP, García NA. The activity of propolis in the scavenging of vitamin B2-photogenerated ROS. Redox Rep. 2015;20(6):246–53. DOI: 10.1179/1351000215Y.0000000033.Mai W., Xu Y., Xu J. Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitis via the ROS/TXNIP Axis // Front Pharmacol. – 2020. – Vol. 11. – P. 185. DOI: 10.3389/fphar.2020.00185.Mai W, Xu Y, Xu J, Zhao D, Ye L, Yu G, Wang Z, Lu Q, Lin J, Yang T, Gu C, Liu S, Zhong Y, Yang H. Berberine Inhibits Nod-Like Receptor Family Pyrin Domain Containing 3 Inflammasome Activation and Pyroptosis in Nonalcoholic Steatohepatitis via the ROS/TXNIP Axis. Front Pharmacol. 2020 Mar 3;11:185. DOI: 10.3389/fphar.2020.00185.Hosseini E., Ghasemzadeh M., Atashibarg M., Haghshenas M. ROS scavenger, N-acetyl-l-cysteine and NOX specific inhibitor, VAS2870 reduce platelets apoptosis while enhancing their viability during storage // Transfusion. – 2019. – Vol. 59, No.4. – P. 1333–1343. DOI: 10.1111/trf.15114.Haghshenas M. ROS scavenger, N-acetyl-l-cysteine and NOX specific inhibitor, VAS2870 reduce platelets apoptosis while enhancing their viability during storage. Transfusion. 2019 Apr; 59(4):1333–43. DOI: 10.1111/trf.15114.Воронков А.В., Поздняков Д.И., Руковицина В.М., Вселова О.Ф., Олохова Е.А., Оганесян Э.Т. Антирадикальные и хелатирующие свойства производных хромон-3-альдегида // Экспериментальная и клиническая фармакология. – 2019. – Т. 82, № 12. – С. 32–35. DOI: 10.30906/0869-2092-2019-82-12-32-35.Pozdnyakov DI, Voronkov AV, Rukovitsyna VM. Chromon-3-aldehyde derivatives restore mitochondrial function in rat cerebral ischemia. Iran J Basic Med Sci. 2020 Sep;23(9):1172–83. DOI: 10.22038/ijbms.2020.46369.10710.Yang C.S., Ho C.T., Zhang J., Wan X., Zhang K., Lim J. Antioxidants: Differing Meanings in Food Science and Health Science // J Agric Food Chem. – 2018. – Vol. 66, No.12. – P. 3063–3068. DOI: 10.1021/acs.jafc.7b05830.Yang CS, Ho CT, Zhang J, Wan X, Zhang K, Lim J. Antioxi-dants: Differing Meanings in Food Science and Health Science. J Agric Food Chem. 2018 Mar 28;66(12):3063–8. DOI: 10.1021/acs.jafc.7b05830.Mohsin N.Ua., Irfan M., Hassan S.U., Saleem U. Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review // Pharm Chem J. – 2020. – Vol. 1. – P. 17. DOI: 10.1007/s11094-020-02187-x.Mohsin NUa, Irfan M, Hassan SU, Saleem U. Current Strategies in Development of New Chromone Derivatives with Diversified Pharmacological Activities: A Review. Pharm Chem J. 2020;1:17. DOI: 10.1007/s11094-020-02187-x.

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