Login Register Cart 0
Generic placeholder image

Current Medicinal Chemistry

Editor-in-Chief

ISSN (Print): 0929-8673
ISSN (Online): 1875-533X

Back
Journal Home About Journal Editorial Board Journal Insight Current Issue Volumes/Issues
Subscribe Translate in Chinese
Research Article

The Effect of Whole Blood and Bone Marrow with the Addition of Pyrimidine-2,4(1h,3h)-dione Thietanyl Derivatives on Free Radical Oxidation

Author(s): Svetlana Meshcheryakova*, Aliya Kayumova, Yang Kang, Alina Shumadalova, Yulia Vinogradova, Dinislam Khuzin, Klara Ziyakaeva, Olga Kiseleva, Irina Gabdulkhakova, Ozal Beylerli, Ilgiz Gareev, Albert Sufianov, Galina Sufianova, Aamir Ahmad, Guang Yang and Zidan Guo*

Volume 30, Issue 17, 2023

Published on: 06 October, 2022

Page: [1993 - 2004] Pages: 12

DOI: 10.2174/0929867329666220805125638

Price: $65

Abstract

Background: It is relevant to study the general patterns and identify non-specific mechanisms of body protective and adaptive reactions violation, which can lead to the various pathological processes and develop principles for the correction of these disorders. One of the therapy and prevention directions is the search for new medicines. In recent years, new derivatives of pyrimidine bases have been synthesized and studied. Pyrimidine-based medicines have a membrane-stabilizing and immunomodulatory effect and can normalize metabolic disorders and increase the oxidative activity of leukocytes. Disruption of the free radical oxidation processes, the generation of reactive oxygen species and lipid peroxidation, including in whole blood and bone marrow, has gained importance in recent years.

Methods: Each reaction was monitored by thin layer chromatography. 1H, 13C, and 15N NMR spectra were recorded (chemical shifts were expressed as δ-values). We studied the effect of 6-methyl-3-(thietan- 3-yl)pyrimidine-2,4(1H,3H)-dione on the generation of reactive oxygen species (ROS) in the whole blood and bone marrow using the study of whole blood spontaneous and stimulated chemiluminescence (CL). CL methods make it possible to quickly and easily assess the studied material (whole blood, bone marrow) effect on free radical oxidation. Using CL methods, it is possible to reveal the presence of medicines' pro- or antioxidant properties, opening up new possibilities in the search for substances with antioxidant properties and comparing their activity.

Results: Alkylation of 6-methylpyrimidine-2,4(1H,3H)-dione by 2-chloromethylthiirane in protic solvents in the presence of alkali leads to the formation of an N-thietane derivative. NMR spectroscopy showed that 6-methylpyrimidine-2,4(1H,3H)-dione was alkylated at position 3. The oxidation reactions of N-(thietan-3-yl)pyrimidine-2,4(1H,3H)-dione were studied, and it was determined that, depending on the excess of the oxidizing agent and the duration of the process, N-(1-oxothietan-3-yl)- or N-(1,1-- dioxothietan-3-yl)pyrimidine-2,4(1H,3H)-diones were formed. The effects of free radical oxidation processes of new biologically active pyrimidine-2,4(1H,3H)-diones were studied.

Conclusion: New pyrimidine-2,4(1H,3H)-diones increase the general adaptive capabilities of the body and have protective effects in extreme conditions.

Keywords: Pyrimidine, thietane, thietanylation, alkylation, free radical oxidation, antioxidant, chemiluminescence.

« Previous
[1]
Arutyunyan, A.A.; Stepanyan, H.M.; Paronikyan, R.V.; Mamyan, S.S. Synthesis and antitumor and antibacterial properties of new N-alkylated pyrimidines. Pharm. Chem. J., 2013, 47(6), 303-306.
[http://dx.doi.org/10.1007/s11094-013-0948-8]
[2]
Gazivoda, T.; Raić-Malić, S.; Marjanović, M.; Kralj, M.; Pavelić, K.; Balzarini, J.; De Clercq, E.; Mintas, M. The novel C-5 aryl, alkenyl, and alkynyl substituted uracil derivatives of L-ascorbic acid: Synthesis, cytostatic, and antiviral activity evaluations. Bioorg. Med. Chem., 2007, 15(2), 749-758.
[http://dx.doi.org/10.1016/j.bmc.2006.10.046] [PMID: 17092728]
[3]
Pizzirani, D.; Pagliuca, C.; Realini, N.; Branduardi, D.; Bottegoni, G.; Mor, M.; Bertozzi, F.; Scarpelli, R.; Piomelli, D.; Bandiera, T. Discovery of a new class of highly potent inhibitors of acid ceramidase: Synthesis and structure-activity relationship (SAR). J. Med. Chem., 2013, 56(9), 3518-3530.
[http://dx.doi.org/10.1021/jm301879g] [PMID: 23614460]
[4]
Lobachev, A.A.; Novikov, M.S.; Ozerov, A.A.; Bukhayt, R.U. Synthesis and antiviral properties for HIV-1 new methylated 1-(benzyloxymethyl)-5-(arylamino)uracil derivatives. Izvestiya vuzov-prikladnaya khimiya i biotekhnologiya, 2011, 1(1), 35-37.
[5]
Geisman, A.N.; Valuev-Elliston, V.T.; Ozerov, A.A.; Khandazhinskaya, A.L.; Chizhov, A.O.; Kochetkov, S.N.; Pannecouque, C.; Naesens, L.; Seley-Radtke, K.L.; Novikov, M.S. 1,6-Bis[(benzyloxy)methyl]uracil derivatives-Novel antivirals with activity against HIV-1 and influenza H1N1 virus. Bioorg. Med. Chem., 2016, 24(11), 2476-2485.
[http://dx.doi.org/10.1016/j.bmc.2016.04.010] [PMID: 27112451]
[6]
Malik, V.; Singh, P.; Kumar, S. Unique chlorine effect in regioselective one-pot synthesis of 1-alkyl-/allyl-3-(o-chlorobenzyl) uracils: Anti-HIV activity of selected uracil derivatives. Tetrahedron, 2006, 62(25), 5944-5951.
[http://dx.doi.org/10.1016/j.tet.2006.04.018]
[7]
Sakakibara, N.; Hamasaki, T.; Baba, M.; Demizu, Y.; Kurihara, M.; Irie, K.; Iwai, M.; Asada, E.; Kato, Y.; Maruyama, T. Synthesis and evaluation of novel 3-(3,5-dimethylbenzyl)uracil analogs as potential anti-HIV-1 agents. Bioorg. Med. Chem., 2013, 21(18), 5900-5906.
[http://dx.doi.org/10.1016/j.bmc.2013.06.061] [PMID: 23916148]
[8]
Fokin, A.V.; Kolomiets, A.F. The chemistry of tiirans; Chemistry: Moscow, 1978.
[9]
Tomashevsky, A.A.; Sokolov, V.V.; Potekhin, A.A. Interaction of (α-haloalkyl) thiiranes with nucleophilic reagents III. Reactions of (α-chloroalkyl) thiiranes and epihalohydrins with phenols. J. Org. Chem., 2003, 39(2), 249-257.
[10]
Gambacorta, A.; Tofani, D.; Loreto, M.A.; Gasperi, T.; Bernini, R. HSAB-driven chemoselective N1-alkylation of pyrimidine bases and their 4-methoxy- or 4-acetylamino-derivatives. Tetrahedron, 2006, 62(29), 6848-6854.
[http://dx.doi.org/10.1016/j.tet.2006.04.098]
[11]
Kataev, V.A.; Meshcheryakova, S.A.; Lazarev, V.V.; Kuznetsov, V.V. Synthesis of thietanyl-substituted pyrimidine-2,4(1H,3H)-dions. Russ. J. Org. Chem., 2013, 49(5), 743-745.
[http://dx.doi.org/10.1134/S1070428013050199]
[12]
Meshcheryakova, S.A.; Kataev, V.A. Synthesis of new thietanylpyrimidine and thietanylimidazole derivatives. Russ. J. Org. Chem., 2013, 49(9), 1358-1360.
[http://dx.doi.org/10.1134/S1070428013090200]
[13]
Vladimirov, IuA.; Proskurina, E.V.; Izmaĭlov, D.Iu. Kinetic chemiluminescence as a method for the study of free radical reactions. Biofizika, 2011, 56(6), 1081-1090.
[PMID: 22279752]
[14]
Farkhutdinov, R.R.; Likhovskikh, V.A. A device for registering chemiluminescence (chemiluminometer - CHL-003). In: Methods for assessing the antioxidant activity of biologically active substances; RUDN: Moscow, 2005; pp. 155-172.
[15]
Calvenor, C.C. Reactions of ethylene sulfides and trithiocarbonates. J. Chem. Soc., 1946, 1946, 1050-1052.
[16]
Gabdulkhakova, I.R.; Kayumova, A.F.; Samokhodova, O.V. The effect of different doses of PCBS on the condition of spontaneous and induced immunoglobulin luminol-dependent chemiluminescence of whole blood. Bashkortostan Med. J., 2016, 1(61), 129-132.
[17]
Zakharov, Y.M.; Rassokhin, A.G. Erythroblastic islet; Medicine: Moscow, 2002.
[18]
Karimov, R.R.; Gabdulkhakova, I.R.; Samokhodova, O.V.; Kayumova, A.F. State of lipid peroxidation and antioxidant protection of red blood cells, bone marrow, serum and liver underpolychlorinated biphenyls intoxication. Bashkortostan Med. J., 2015, 10(6), 44-48.
[19]
Startbase library. Available from: www.startbase.ru/knowledge/articles/152/ (Accessed on: December 23, 2021).
[20]
Sokolov, V.V.; Butkevich, A.N.; Yuskovets, V.N.; Tomashevskii, A.A.; Potekhin, A.A. Reactions of 2-(α-Haloalkyl)thiiranes with nucleophilic reagents: IV. Alkylation of Sulfonamides with 2-Chloromethylthiirane. Synthesis and properties of 3-(Arylamino)thietanes. Russ. J. Org. Chem., 2005, 41, 1023-1035.
[http://dx.doi.org/10.1007/s11178-005-0288-6]
[21]
Block, E.; Katritzky, A.R.; Rees, C.W. Thietanes. Thietes and fuser-ring derivatives. Compr. Heterocyclic Chem., 1997, 7, 403-448.
[22]
Meshcheryakova, S.A.; Kataev, V.A.; Munasipova, D.A.; Fattakhova, I.Y. Oxidation and isomerism of thietane-containing heterocycles. Russ. J. Gen. Chem., 2014, 84(5), 865-868.
[http://dx.doi.org/10.1134/S1070363214050144]
[23]
Contreras, J.G.; Hurtado, S.M.; Gerli, L.A.; Madariaga, S.T. Cis and trans conformations in 3-substituted thietane-1-oxide. J. Mol. Struct. Theochem., 2005, 713, 207-213.
[http://dx.doi.org/10.1016/j.theochem.2004.10.014]
[24]
Contreras, J.G.; Madariaga, S.T. Mechanism of trans-cis isomerization reaction in 3-substituted thietane-1-oxide. J. Mol. Struct. Theochem., 2001, 572, 235-242.
[http://dx.doi.org/10.1016/S0166-1280(01)00635-2]
[25]
Gracheva, T.A. Improvement of the chemiluminescent method for studying the functional activity of phagocytic cells. Clin. Diagn. Lab., 2008, 2, 54-55.
[26]
Blazheevskly, M.Y.; Bondarenco, N.Y. Chemiluminescence-based kinetic determination of drug. Chem. Anal. Methods, 2011, 6(3), 124-142.
[27]
Shchulkin, A.V. A modern concept of antihypoxic and antioxidant effects of mexidol. Zh. Nevrol. Psikhiatr. Im. S. S. Korsakova, 2018, 118(12. Vyp. 2), 87-93.
[http://dx.doi.org/10.17116/jnevro201811812287] [PMID: 30830123]
[28]
Merck products. Available from: www.sigmaaldrich.com/catalog/search/ProductDetail/SIGMA/Z4250 (Accessed on: December 23, 2021).

Rights & Permissions Print Cite
Article Metrics
37
2
Wayfinder Image
World Antimicrobial Awareness Week
© 2024 Bentham Science Publishers | Privacy Policy