DOI: https://doi.org/10.22263/2312-4156.2020.5.27
Veiko A.G.
Molecular structure, quantum-chemical parameters, mechanism of cytoprotective effect and the contribution of functional groups to antioxidant potential of flavonoids
Grodno State University named after Yanka Kupala, Grodno, Republic of Belarus
Vestnik VGMU. 2020;19(5):27-39.
Abstract.
Numerous diseases (inflammation, diabetes, vascular lesions, etc.) are known to be associated with an increased level of the oxidative stress, and as a consequence, with metabolic disorders.
In this connection, in biochemistry, medicine and pharmacy, the search for effective and safe synthetic and natural antioxidants for the prevention of pathologies, mediated by an excess of oxidative processes and reactive oxygen species (ROS), is the important task.
Plant components, such as flavonoids, can produce pronounced antioxidant effect, and demonstrate beneficial pharmacological and biochemical activities.
In the present study, a comparative assessment of the quantum-chemical parameters and antioxidant activity of a number of flavonoids (catechin, quercetin, naringenin), differing in their molecular structure and having various functional groups in a model system has been made.
The flavonoids prevented the development of lipid peroxidation of rat erythrocyte membranes, induced by tert-butylhydroperoxide (tBHP). The effective concentration IC50 of inhibition of this process is: in case of quercetin 9.74±0.8 μM, catechin 8.84±0.7 μM, naringenin 46.8±4.4 μM. The flavonoids also partially inhibited glutathione oxidation in the erythrocyte cytoplasm.
The article presents an analysis of the chemical structures of the flavonoids: catechin, quercetin, and naringenin based on molecular modelling and quantum-chemical calculations.
The obtained results can be used to evaluate the biological potential of molecules with similar functional groups and structural features, as well as to conduct further research and to do pharmacological screening of biologic active compounds.
Key words: flavonoids, molecular structure, quantum chemistry, functional groups, antioxidants.
References
1. Frijhoff J, Winyard PG, Zarkovic N, Davies SS, Stocker R, Cheng D, et al. Clinical relevance of biomarkers of oxidative stress. Antioxid Redox Signal. 2015 Nov;23(14):1144-70. doi: http://dx.doi.org/10.1089/ars.2015.6317
2. Griendling KK, FitzGerald GA. Oxidative stress and cardiovascular injury: Part I: basic mechanisms and in vivo monitoring of ROS. Circulation. 2003 Oct;108(16):1912-6. doi: http://dx.doi.org/10.1161/01.CIR.0000093660.86242.BB
3. Ischiropoulos H, Beckman JS. Oxidative stress and nitration in neurodegeneration: cause, effect, or association? J Clin Invest. 2003 Jan;111(2):163-9. doi: http://dx.doi.org/10.1172/JCI17638
4. Ceriello A. Oxidative stress and diabetes-associated complications. Endocr Pract. 2006 Jan-Feb;12 Suppl 1:60-2. doi: http://dx.doi.org/10.4158/EP.12.S1.60
5. Susanne Karbach, Philip Wenzel, Ari Waisman, Thomas Munzel, Andreas Daiber. eNOS uncoupling in cardiovascular diseases-the role of oxidative stress and inflammation. Curr Pharm Des. 2014;20(22):3579-94. doi: http://dx.doi.org/10.2174/13816128113196660748
6. Brieger K, Schiavone S, Miller FJ, Krause K-H. Reactive oxygen species: from health to disease. Swiss Med Wkly. 2012 Aug;142:w13659. doi: http://dx.doi.org/10.4414/smw.2012.13659
7. Hritcu L, Ionita R, Postu PA, Gupta GK, Turkez H, Lima TC, Uchôa C, et al. Antidepressant Flavonoids and Their Relationship with Oxidative Stress. Oxid Med Cell. Longev. 2017;2017(118). doi: http://dx.doi.org/10.1155/2017/5762172
8. Winkel-Shirley B. Flavonoid Biosynthesis. A Colorful Model for Genetics, Biochemistry, Cell Biology, and Biotechnology. Plant Physiol. 2001 Jun;126(2):485-93. doi: http://dx.doi.org/10.1104/pp.126.2.485
9. Kozłowska J, Grela E, Baczyńska D, Grabowiecka A, Anioł M. Novel O-alkyl Derivatives of Naringenin and Their Oximes with Antimicrobial and Anticancer Activity. Molecules. 2019 Feb;24(4):679. doi: http://dx.doi.org/10.3390/molecules24040679
10. Fuhr U, Klittich K, Staib AH. Inhibitory effect of grapefruit juice and its bitter principal, naringenin, on CYP1A2 dependent metabolism of caffeine in man. Br J Clin Pharmacol. 1993 Apr;35(4):431-6. doi: http://dx.doi.org/10.1111/j.1365-2125.1993.tb04162.x
11. Hernández-Aquino E, Muriel P. Beneficial effects of naringenin in liver diseases: Molecular mechanisms. World J Gastroenterol. 2018 Apr;24(16):1679-1707. doi: http://dx.doi.org/10.3748/wjg.v24.i16.1679
12. Mangels DR, Mohler ER. Catechins as potential mediators of cardiovascular health. Arterioscler Thromb Vasc Biol. 2017 May;37(5):757-763. doi: http://dx.doi.org/10.1161/ATVBAHA.117.309048
13. Bernatoniene J, Kopustinskiene DM. The Role of Catechins in Cellular Responses to Oxidative Stress. Molecules. 2018 Apr 20;23(4):965. doi: http://dx.doi.org/10.3390/molecules23040965
14. Abdelkawy KS, Balyshev ME, Elbarbry F. A new validated HPLC method for the determination of quercetin: Application to study pharmacokinetics in rats. Biomed Chromatogr. 2017 Mar;31(3). doi: http://dx.doi.org/10.1002/bmc.3819
15. Eid HM, Haddad PS. The Antidiabetic Potential of Quercetin: Underlying Mechanisms. Curr Med Chem. 2017;24(4):355-364. doi: http://dx.doi.org/10.2174/0929867323666160909153707
16. D’Andrea G. Quercetin: A flavonol with multifaceted therapeutic applications? Fitoterapia. 2015 Oct;106:256-71. doi: http://dx.doi.org/10.1016/j.fitote.2015.09.018
17. Zhou J, Fang L, Liao J, Li L, Yao W, Xiong Z, et al. Investigation of the anti-cancer effect of quercetin on HepG2 cells in vivo. PLoS One. 2017 Mar;12(3):e0172838. doi: http://dx.doi.org/10.1371/journal.pone.0172838
18. Strugała P, Tronina T, Huszcza E, Gabrielska J. Bioactivity In Vitro of Quercetin Glycoside Obtained in Beauveria bassiana Culture and Its Interaction with Liposome Membranes. Molecules. 2017 Sep;22(9):1520. doi: http://dx.doi.org/10.3390/molecules22091520
19. Veiko AG. Computer modeling of the structure and properties of biologically active compounds and drugs. Pharmacology in silico. Novosti Med-Biol Nauk. 2019;19(3):117-32. (In Russ.)
20. Stocks J, Dormandy TL. The autoxidation of human red cell lipids induced by hydrogen peroxide. Br J Haematol. 1971 Jan;20(1):95-111. doi: http://dx.doi.org/10.1111/j.1365-2141.1971.tb00790.x
21. Akerboom TP, Sies H. Assay of glutathione, glutathione disulfide, and glutathione mixed disulfides in biological samples. Methods Enzymol. 1981;77:373-82. doi: http://dx.doi.org/10.1016/s0076-6879(81)77050-2
22. Chemistry Software, HyperChem, Molecular Modeling. Available from: http://www.hyper.com/ [Accessed 27 Oct 2020]
23. Onishi T. Quantum Computational Chemistry: Modelling and Calculation for Functional Materials. Singapore: Springe; 2018. 290 p.
24. Babaie-Kafaki S, Ghanbari R. A descent extension of the Polak–Ribière–Polyak conjugate gradient method. Comput Math Appl. 2014 Dec;68(12 Part A):2005-11. doi: http://dx.doi.org/10.1016/j.camwa.2014.09.019
25. Campbell MJ, Machin D, Walters SJ. Medical Statistics: A Textbook for the Health Sciences. Hoboken, NJ, United States: John Wiley & Sons; 2010. 347 p.
26. Kučera O, Endlicher R, Roušar T, Lotková H, Garnol T, Drahota Z, et al. The Effect of tert-Butyl Hydroperoxide-Induced Oxidative Stress on Lean and Steatotic Rat Hepatocytes In Vitro. Oxid Med Cell Longev. 2014;2014:752506. doi: http://dx.doi.org/10.1155/2014/752506
27. Enami S, Sakamoto Y, Colussi AJ. Fenton chemistry at aqueous interfaces. Proc Natl Acad Sci U S A. 2014 Jan;111(2):623-8. doi: http://dx.doi.org/10.1073/pnas.1314885111
28. Sarian MN, Ahmed QU, So'ad SZM, Alhassan AM, Murugesu S, Perumal V, et al. Antioxidant and Antidiabetic Effects of Flavonoids: A Structure-Activity Relationship Based Study. Biomed Res Int. 2017;2017:8386065. doi: http://dx.doi.org/10.1155/2017/8386065
29. Yordi EG, Pérez EM, Matos MJ, Villares EU. Antioxidant and pro-oxidant effects of polyphenolic compounds and structure-activity relationship evidence. In: Bouayed J, Bohn T, editors. Nutrition, well-being and health. Rijeka: InTech; 2012. P.23-48. doi: http://dx.doi.org/10.5772/29471
30. Wen J, Liu B, Yuan E, Ma Y, Yongyi Z. Preparation and Physicochemical Properties of the Complex of Naringenin with Hydroxypropyl-β-Cyclodextrin. Molecules. 2010 Jun;15(6):4401-7. doi: http://dx.doi.org/10.3390/molecules15064401
31. Srinivas K, King JW, Howard LR, Monrad JK. Solubility of Gallic Acid, Catechin, and Protocatechuic Acid in Subcritical Water from (298.75 to 415.85) K. J Chem Eng Data. 2010;55(9):3101-8. doi: http://dx.doi.org/10.1021/je901097n
32. Scheidta HA, Pampel A, Nissler L, Gebhardtc R, Huster D. Investigation of the membrane localization and distribution of flavonoids by high-resolution magic angle spinning NMR spectroscopy. Biochim Biophys Acta (BBA) – Biomembr. 2004 May;1663(1-2): 97-107. doi: http://dx.doi.org/10.1016/j.bbamem.2004.02.004
33. Veiko AG, Ilich TV, Lapshina EA, Buko VU, Zavodnik IB. Quantum-chemical modeling of the electronic structure of quercetin and inhibition of lipid peroxidation in mitochondria and erythrocytes of rats by quercetin and the quercetin-hydroxypropyl-β-cyclodextrin complex. Izv Nats Akad Nauk Belarusi Ser Biol Nauk. 2018;63(4):500-12. (In Russ.)
34. Oleinik LI, Buslova TS, Veselova IA, Shekhovtcova TN. Kinetics of peroxidase oxidation of quercetin in the presence of P-cyclodextrin. Vest Mosk Un-ta Ser 2 Khimiia. 2011;52(3):199-203. (In Russ.)
Information about authors:
Veiko A.G. – postgraduate of the Chair of Biochemistry, Grodno State University named after Yanka Kupala.
Correspondence address: Republic of Belarus, 230030, Grodno, 50 Leninskogo Komsomola blvd., Grodno State University named after Yanka Kupala, Chair of Biochemistry. E-mail: Этот адрес электронной почты защищён от спам-ботов. У вас должен быть включен JavaScript для просмотра. – Artem G. Veiko.
