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Medicinal Chemistry

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ISSN (Print): 1573-4064
ISSN (Online): 1875-6638

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Research Article

Synthesis, Cytotoxicity and Antiviral Activity Against Vaccinia Virus of 2-(3-Coumarinyl)-1-Hydroxyimidazoles

Author(s): Polina A. Nikitina*, Anastasia M. Zakharova, Olga A. Serova, Nikolay I. Bormotov, Oleg Y. Mazurkov, Larisa N. Shishkina, Tatiana Y. Koldaeva, Elizaveta I. Basanova and Valery P. Perevalov

Volume 19, Issue 5, 2023

Published on: 30 December, 2022

Page: [468 - 477] Pages: 10

DOI: 10.2174/1573406419666221125101053

Price: $65

Abstract

Background: In 1980, smallpox became the first viral disease eradicated through vaccination. After the termination of the Smallpox Eradication Program, the global immunization of the population also ceased. Now, most people do not have any immunity against infections caused by orthopoxviruses. Emerging cases of zoonotic orthopox infections transferring to humans inspire the search for new small organic molecules possessing antiviral activity against orthopoxviruses.

Objective: Here, we present the synthesis and evaluation of antiviral activity against one of the orthopoxviruses, i.e., Vaccinia virus, of hybrid structures containing 1-hydroxyimidazole and benzopyranone moieties.

Methods: Novel 2-(3-coumarinyl)-1-hydroxyimidazoles were synthesized. Their prototropic tautomerism was considered using 1H NMR spectroscopy. Antiviral activity of both new 2-(3-coumarinyl)- 1-hydroxyimidazoles and previously described 2-(3-chromenyl)-1-hydroxyimidazoles against Vaccinia virus was evaluated in Vero cell culture.

Results: Newly synthesized 2-(3-coumarinyl)-1-hydroxyimidazoles existed in CDCl3 as a mixture of prototropic tautomers (N-hydroxyimidazole and imidazole N-oxide), transition to DMSO-d6 resulting in the prevalence of N-oxide tautomer. Evaluation of cytotoxicity and antiviral activity against Vaccinia virus was performed in Vero cell culture. Compounds possessing high antiviral activity were present in both series. It was demonstrated that the structure of heterocyclic substituent in position 2 of imidazole impacted the cytotoxicity of substances under consideration. Thus, molecules containing coumarin moiety exhibited lower toxicity than similarly substituted 2-(3-chromenyl)-1- hydroxyimidazoles.

Conclusion: Perspective virus inhibiting compounds possessing antiviral activity against Vaccinia virus were revealed in the series of 2-(3-coumarinyl)-1-hydroxyimidazoles.

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[1]
Meyer, H.; Ehmann, R.; Smith, G.L. Smallpox in the post-eradication era. Viruses, 2020, 12(2), 138.
[http://dx.doi.org/10.3390/v12020138] [PMID: 31991671]
[2]
Silva, N.I.O.; de Oliveira, J.S.; Kroon, E.G.; Trindade, G.S.; Drumond, B.P. Here, there, and everywhere: The wide host range and geographic distribution of zoonotic orthopoxviruses. Viruses, 2020, 13(1), 43.
[http://dx.doi.org/10.3390/v13010043] [PMID: 35062247]
[3]
Krankowska, D.C. Woźniak, P.A.; Cybula, A.; Izdebska, J.; Suchacz, M.; Samelska, K.; Wiercińska-Drapało, A.; Szaflik, J.P. Cowpox: How dangerous could it be for humans? Case report. Int. J. Infect. Dis., 2021, 104, 239-241.
[http://dx.doi.org/10.1016/j.ijid.2020.12.061] [PMID: 33359672]
[4]
Guagliardo, S.A.J.; Monroe, B.; Moundjoa, C.; Athanase, A.; Okpu, G.; Burgado, J.; Townsend, M.B.; Satheshkumar, P.S.; Epperson, S.; Doty, J.B.; Reynolds, M.G.; Dibongue, E.; Etoundi, G.A.; Mathieu, E.; McCollum, A.M. Asymptomatic orthopoxvirus circulation in humans in the wake of a monkeypox outbreak among chimpanzees in cameroon. Am. J. Trop. Med. Hyg., 2020, 102(1), 206-212.
[http://dx.doi.org/10.4269/ajtmh.19-0467] [PMID: 31769389]
[5]
Hughes, C.M.; Liu, L.; Davidson, W.B.; Radford, K.W.; Wilkins, K.; Monroe, B.; Metcalfe, M.G.; Likafi, T.; Lushima, R.S.; Kabamba, J.; Nguete, B.; Malekani, J.; Pukuta, E.; Karhemere, S.; Muyembe Tamfum, J.J.; Okitolonda Wemakoy, E.; Reynolds, M.G.; Schmid, D.S.; McCollum, A.M. A tale of two viruses: Coinfections of monkeypox and varicella zoster virus in the democratic republic of congo. Am. J. Trop. Med. Hyg., 2021, 104(2), 604-611.
[http://dx.doi.org/10.4269/ajtmh.20-0589] [PMID: 33289470]
[6]
Sarwar, S.; Maskey, U.; Thada, P.K.; Mustansir, M.; Sarfraz, A.; Sarfraz, Z. Re-emergence of monkeypox amidst delta variant concerns: A point of contention for public health virology? J. Med. Virol., 2022, 94(3), 805-806.
[http://dx.doi.org/10.1002/jmv.27306] [PMID: 34453755]
[7]
Bunge, E.M.; Hoet, B.; Chen, L.; Lienert, F.; Weidenthaler, H.; Baer, L.R.; Steffen, R. The changing epidemiology of human monkeypox—A potential threat? A systematic review. PLoS Negl. Trop. Dis., 2022, 16(2), e0010141.
[http://dx.doi.org/10.1371/journal.pntd.0010141] [PMID: 35148313]
[8]
José da Silva Domingos, I.; Silva de Oliveira, J.; Lorene Soares Rocha, K.; Bretas de Oliveira, D.; Geessien Kroon, E.; Barbosa Costa, G.; de Souza Trindade, G. Twenty years after bovine vaccinia in Brazil: Where we are and where are we going? Pathogens, 2021, 10(4), 406.
[http://dx.doi.org/10.3390/pathogens10040406] [PMID: 33807254]
[9]
Shchelkunov, S.N.; Shchelkunova, G.A. We should be prepared to smallpox re-emergence. Prob. Virol., Russian j., 2019, 64(5), 206-214. http://dx.doi.org/10.36233/0507-4088-2019-64-5-206-214
[10]
Gallwitz, S.; Schutzbank, T.; Heberling, R.L.; Kalter, S.S.; Galpin, J.E. Smallpox: Residual antibody after vaccination. J. Clin. Microbiol., 2003, 41(9), 4068-4070.
[http://dx.doi.org/10.1128/JCM.41.9.4068-4070.2003] [PMID: 12958227]
[11]
MacIntyre, C.R. Reevaluating the risk of smallpox reemergence. Mil. Med., 2020, 185(7-8), e952-e957.
[http://dx.doi.org/10.1093/milmed/usaa084] [PMID: 32373931]
[12]
Andrei, G.; Snoeck, R. Cidofovir activity against poxvirus infections. Viruses, 2010, 2(12), 2803-2830.
[http://dx.doi.org/10.3390/v2122803] [PMID: 21994641]
[13]
Jordan, R.; Leeds, J.M.; Tyavanagimatt, S.; Hruby, D.E. Development of ST-246® for treatment of poxvirus infections. Viruses, 2010, 2(11), 2409-2435.
[http://dx.doi.org/10.3390/v2112409] [PMID: 21994624]
[14]
Chan-Tack, K.; Harrington, P.; Bensman, T.; Choi, S.Y.; Donaldson, E.; O’Rear, J.; McMillan, D.; Myers, L.; Seaton, M.; Ghantous, H.; Cao, Y.; Valappil, T.; Birnkrant, D.; Struble, K. Benefit-risk assessment for brincidofovir for the treatment of smallpox: U.S. Food and drug administration’s evaluation. Antiviral Res., 2021, 195, 105182.
[http://dx.doi.org/10.1016/j.antiviral.2021.105182] [PMID: 34582915]
[15]
Russo, A.T.; Grosenbach, D.W.; Chinsangaram, J.; Honeychurch, K.M.; Long, P.G.; Lovejoy, C.; Maiti, B.; Meara, I.; Hruby, D.E. An overview of tecovirimat for smallpox treatment and expanded anti-orthopoxvirus applications. Expert Rev. Anti Infect. Ther., 2021, 19(3), 331-344.
[http://dx.doi.org/10.1080/14787210.2020.1819791] [PMID: 32882158]
[16]
Mazurkov, O.Y.; Kabanov, A.S.; Shishkina, L.N.; Sergeev, A.A.; Skarnovich, M.O.; Bormotov, N.I.; Skarnovich, M.A.; Ovchinnikova, A.S.; Titova, K.A.; Galahova, D.O.; Bulychev, L.E.; Sergeev, A.A.; Taranov, O.S.; Selivanov, B.A.; Tikhonov, A.Y.; Zavjalov, E.L.; Agafonov, A.P.; Sergeev, A.N. New effective chemically synthesized anti-smallpox compound NIOCH-14. J. Gen. Virol., 2016, 97(5), 1229-1239.
[http://dx.doi.org/10.1099/jgv.0.000422] [PMID: 26861777]
[17]
Mazurkov, O.Y.; Shishkina, L.N.; Bormotov, N.I.; Skarnovich, M.O.; Serova, O.A.; Mazurkova, N.A.; Chernonosov, A.A.; Tikhonov, A.Y.; Selivanov, B.A. Estimation of absolute bioavailability of the chemical substance of the anti-smallpox preparation NIOCH-14 in mice. Bull. Exp. Biol. Med., 2020, 170(2), 207-210.
[http://dx.doi.org/10.1007/s10517-020-05034-x] [PMID: 33263846]
[18]
Zemtsova, M.N.; Zimichev, A.V.; Trakhtenberg, P.L.; Klimochkin, Y.N.; Leonova, M.V.; Balakhnin, S.M.; Bormotov, N.I.; Serova, O.A.; Belanov, E.F. Synthesis and antiviral activity of several quinoline derivatives. Pharm. Chem. J., 2011, 45(5), 267-269.
[http://dx.doi.org/10.1007/s11094-011-0613-z]
[19]
Moiseev, I.K.; Kon’kov, S.A.; Ovchinnikov, K.A.; Kilyaeva, N.M.; Bormasheva, K.M.; Nechaeva, O.N.; Leonova, M.V.; Klimochkin, Y.N.; Balakhnin, S.M.; Bormotov, N.I.; Serova, O.A.; Belanov, E.F. Synthesis and antiviral activity of new adamantane derivatives. Pharm. Chem. J., 2012, 45(10), 588-592.
[http://dx.doi.org/10.1007/s11094-012-0686-3]
[20]
Shiryaev, V.A.; Skomorohov, M.Y.; Leonova, M.V.; Bormotov, N.I.; Serova, O.A.; Shishkina, L.N.; Agafonov, A.P.; Maksyutov, R.A.; Klimochkin, Y.N. Adamantane derivatives as potential inhibitors of p37 major envelope protein and poxvirus reproduction. Design, synthesis and antiviral activity. Eur. J. Med. Chem., 2021, 221, 113485.
[http://dx.doi.org/10.1016/j.ejmech.2021.113485] [PMID: 33965861]
[21]
Rusinov, V.L.; Egorov, I.N.; Chupakhin, O.N.; Belanov, E.F.; Bormotov, N.I.; Serova, O.A. Synthesis and antiviral activity of 1,2,4-triazine derivatives. Pharm. Chem. J., 2012, 45(11), 655-659.
[http://dx.doi.org/10.1007/s11094-012-0698-z]
[22]
Sokolova, A.S.; Yarovaya, O.I.; Bormotov, N.I.; Shishkina, L.N.; Salakhutdinov, N.F. Synthesis and antiviral activity of camphor-based 1,3-thiazolidin-4-one and thiazole derivatives as Orthopoxvirus -reproduction inhibitors. MedChemComm, 2018, 9(10), 1746-1753.
[http://dx.doi.org/10.1039/C8MD00347E] [PMID: 30429979]
[23]
Sokolova, A.S.; Yarovaya, O.I.; Bormotov, N.I.; Shishkina, L.N.; Salakhutdinov, N.F. Discovery of a new class of inhibitors of vaccinia virus based on (−)-borneol from Abies sibirica and (+)-camphor. Chem. Biodivers., 2018, 15(9), e1800153.
[http://dx.doi.org/10.1002/cbdv.201800153] [PMID: 29956885]
[24]
Suslov, E.V.; Mozhaytsev, E.S.; Korchagina, D.V.; Bormotov, N.I.; Yarovaya, O.I.; Volcho, K.P.; Serova, O.A.; Agafonov, A.P.; Maksyutov, R.A.; Shishkina, L.N.; Salakhutdinov, N.F. New chemical agents based on adamantane–monoterpene conjugates against orthopoxvirus infections. RSC Medicinal Chemistry, 2020, 11(10), 1185-1195.
[http://dx.doi.org/10.1039/D0MD00108B] [PMID: 33479623]
[25]
Sokolova, A.S. Kovaleva, K.S.; Yarovaya, O.I.; Bormotov, N.I.; Shishkina, L.N.; Serova, O.A.; Sergeev, A.A.; Agafonov, A.P.; Maksuytov, R.A.; Salakhutdinov, N.F. (+)-Camphor and (−)‐borneol derivatives as potential anti-orthopoxvirus agents. Arch. Pharm., 2021, 354(6), 2100038.
[http://dx.doi.org/10.1002/ardp.202100038] [PMID: 33605479]
[26]
Sokolova, A.S.; Putilova, V.P.; Yarovaya, O.I.; Zybkina, A.V.; Mordvinova, E.D.; Zaykovskaya, A.V.; Shcherbakov, D.N.; Orshanskaya, I.R.; Sinegubova, E.O.; Esaulkova, I.L.; Borisevich, S.S.; Bormotov, N.I.; Shishkina, L.N.; Zarubaev, V.V.; Pyankov, O.V.; Maksyutov, R.A.; Salakhutdinov, N.F. Synthesis and antiviral activity of camphene derivatives against different types of viruses. Molecules, 2021, 26(8), 2235.
[http://dx.doi.org/10.3390/molecules26082235] [PMID: 33924393]
[27]
Sokolova, A.S.; Kovaleva, K.S.; Kuranov, S.O.; Bormotov, N.I.; Borisevich, S.S.; Zhukovets, A.A.; Yarovaya, O.I.; Serova, O.A.; Nawrozkij, M.B.; Vernigora, A.A.; Davidenko, A.V.; Khamitov, E.M.; Peshkov, R.Y.; Shishkina, L.N.; Maksuytov, R.A.; Salakhutdinov, N.F. Design, synthesis and biological evaluation of novel (+)-camphor and (-)-fenchone based derivatives as potente orthopoxviruses inhibitors. ChemMedChem, 2022, 17(12), e202100771.
[http://dx.doi.org/10.1002/cmdc.202100771] [PMID: 35388614]
[28]
Nikitina, P.A.; Bormotov, N.I.; Shishkina, L.N.; Tikhonov, A.Y.; Perevalov, V.P. Synthesis and antiviral activity of 1-hydroxy-2-(2-hydroxyphenyl)imidazoles against vaccinia virus. Russ. Chem. Bull., 2019, 68(3), 634-637.
[http://dx.doi.org/10.1007/s11172-019-2467-6]
[29]
Tsay, S.C.; Lin, S.Y.; Huang, W.C.; Hsu, M.H.; Hwang, K.; Lin, C.C.; Horng, J.C.; Chen, I.C.; Hwu, J.; Shieh, F.K.; Leyssen, P.; Neyts, J. Synthesis and structure-activity relationships of imidazole-coumarin conjugates against Hepatitis C virus. Molecules, 2016, 21(2), 228.
[http://dx.doi.org/10.3390/molecules21020228] [PMID: 26901180]
[30]
Liu, G.; Wang, C.; Wang, H.; Zhu, L.; Zhang, H.; Wang, Y.; Pei, C.; Liu, L. Antiviral efficiency of a coumarin derivative on spring viremia of carp virus in vivo. Virus Res., 2019, 268, 11-17.
[http://dx.doi.org/10.1016/j.virusres.2019.05.007] [PMID: 31095989]
[31]
Liu, L.; Hu, Y.; Lu, J.; Wang, G. An imidazole coumarin derivative enhances the antiviral response to spring viremia of carp virus infection in zebrafish. Virus Res., 2019, 263, 112-118.
[http://dx.doi.org/10.1016/j.virusres.2019.01.009] [PMID: 30658072]
[32]
Hu, Y.; Chen, W.; Shen, Y.; Zhu, B.; Wang, G.X. Synthesis and antiviral activity of coumarin derivatives against infectious hematopoietic necrosis virus. Bioorg. Med. Chem. Lett., 2019, 29(14), 1749-1755.
[http://dx.doi.org/10.1016/j.bmcl.2019.05.019] [PMID: 31104994]
[33]
Shcherbakov, K.V.; Artemyeva, M.A.; Burgart, Y.V.; Saloutin, V.I.; Volobueva, A.S.; Misiurina, M.A.; Esaulkova, Y.L.; Sinegubova, E.O.; Zarubaev, V.V. 7-Imidazolyl-substituted 4′-methoxy and 3′,4′-dimethoxy-containing polyfluoroflavones as promising antiviral agents. J. Fluor. Chem., 2020, 240, 109657.
[http://dx.doi.org/10.1016/j.jfluchem.2020.109657] [PMID: 33071313]
[34]
Olomola, T.O.; Klein, R.; Kaye, P.T. Convenient synthesis of 3-methylcoumarins and coumarin-3-carbaldehydes. Synth. Commun., 2012, 42(2), 251-257.
[http://dx.doi.org/10.1080/00397911.2010.523491]
[35]
Bochkov, A.Y.; Akchurin, I.O.; Traven, V.F. A new facile way for the preparation of 3-formylcoumarins. Heterocycl. Commun., 2017, 23(2), 75-78.
[http://dx.doi.org/10.1515/hc-2017-0038]
[36]
Selivanov, B.A.; Tikhonov, A.Y.; Belanov, E.F.; Bormotov, N.I.; Kabanov, A.S.; Mazurkov, O.Y.; Serova, O.A.; Shishkina, L.N.; Agafonov, A.P.; Sergeev, A.N. Synthesis and antiviral activity of 1-aryl-3-(3,5-dioxo-4-azatetracyclo[5.3.2.02,6.08,10]dodec-11-en-4-yl)ureas. Pharm. Chem. J., 2017, 51(6), 439-443.
[http://dx.doi.org/10.1007/s11094-017-1629-9]
[37]
Bailey, T.R.; Rippin, S.R.; Opsitnick, E.; Burns, C.J.; Pevear, D.C.; Collett, M.S.; Rhodes, G.; Tohan, S.; Huggins, J.W.; Baker, R.O.; Kern, E.R.; Keith, K.A.; Dai, D.; Yang, G.; Hruby, D.; Jordan, R.N -(3,3a,4,4a,5,5a,6,6a-Octahydro-1,3-dioxo-4,6- ethenocycloprop[f]isoindol-2-(1 H)-yl)carboxamides: Identification of Novel Orthopoxvirus Egress Inhibitors. J. Med. Chem., 2007, 50(7), 1442-1444.
[http://dx.doi.org/10.1021/jm061484y] [PMID: 17335190]
[38]
Rukovodstvo po provedeniyu doklinicheskikh issledovaniy lekarstvennykh sredstv; Mironov, A.N., Ed.; Grif & Co: Moscow, 2012.
[39]
Nikitina, P.A.; Perevalov, V.P. Methods of synthesis and physicochemical properties of 1-hydroxyimidazoles, imidazole 3-oxides, and their benzoannulated analogs. Chem. Heterocycl. Compd., 2017, 53(2), 123-149.
[http://dx.doi.org/10.1007/s10593-017-2030-z]
[40]
Nikitina, P.A.; Kuz’mina, L.G.; Perevalov, V.P.; Tkach, I.I. Synthesis and study of prototropic tautomerism of 2-(3-chromenyl)-1-hydroxyimidazoles. Tetrahedron, 2013, 69(15), 3249-3256.
[http://dx.doi.org/10.1016/j.tet.2013.02.039]
[41]
Nikitina, P.A.; Koldaeva, T.Y.; Mityanov, V.S.; Miroshnikov, V.S.; Basanova, E.I.; Perevalov, V.P. Prototropic tautomerism and some features of the IR spectra of 2-(3-Chromenyl)-1-hydroxyimidazoles. Aust. J. Chem., 2019, 72(9), 699-708.
[http://dx.doi.org/10.1071/CH19222]

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