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ISSN 2522-9028 (Print)
ISSN 2522-9036 (Online)

Fiziologichnyi Zhurnal

is a scientific journal issued by the

Bogomoletz Institute of Physiology
National Academy of Sciences of Ukraine

Editor-in-chief: V.F. Sagach

The journal was founded in 1955 as
1955 – 1977 "Fiziolohichnyi zhurnal" (ISSN 0015 – 3311)
1978 – 1993 "Fiziologicheskii zhurnal" (ISSN 0201 – 8489)
1994 – 2016 "Fiziolohichnyi zhurnal" (ISSN 0201 – 8489)
2017 – "Fiziolohichnyi zhurnal" (ISSN 2522-9028)

Fiziol. Zh. 2012; 58(1): 36-42

The antiviral activity of diphenyl derivatives in different model systems

Bogorad-Kobel's'ka OS, Zholobak NM, Olevins'ka ZM, Spivak MIa

    D.K. Zabolotnyi Institute of microbiology and virusology NAS of Ukraine, Kyiv, Ukraine


In experiments on two model systems L929/VSV and RF/ HSV-1 in vitro we have studied the antiviral activity of new structural analogues of tilorone - 4,4'-bis[2-(diethyl-amino)ethoxy]diphenyl dihydrochloride and 2-methoxy-carbonyl-4-4'-bis[2-(diethylamino)ethoxy]diphenyl dihydro-chloride. In experiments the tested substances were adminis­tered in preventive and therapeutic schemes. The preventive scheme confirms the existence of a correlation between IFN production under the influence of tested substances and their antiviral activity. It is shown that diphenyls are able to inhibit the development of viral cytopathic effect induced by DNA-and RNA-containing viruses. Diphenyl derivatives are less toxic than tilorone and could be considered as promising sub­stances for further research to develop new antiviral drugs.

Keywords: amixine .N, tilorone, diphenyl derivatives, antiviralactivity, DNA-containing viruses, RNA-containing viruses.


  1. Andronati S.A., Litvinova L.A., Golovenka N.Ya. Oral inducer of endogenous interferon Amiksin and its analogues . Zh. AMS of Ukraine. 1999. 5, No. 1. S. 53-66.
  3. Bogatsky O.V., Gren A.I., Litvinova L.O., Lem-part G.V. About the synthesis of 2,7-bis- [2- (diethylamino) ethoxy-fluoren-9-one . Add. ANURSR. Ser. B. 1976. N 7. FROM. 610-612.
  5. Votyakov V.I., Boreko E.I., Vladyko G.V., Karako N.I., Galegov G.A., Leont'ev N.A. The primary study of the antiviral properties of synthetic and natural compounds . Method. recommendations. Minsk, 1986.- 25 s.
  7. Doklinichni doslidzhennya likarsky zasobiv. Method. Recommendations . Ed. Corresponding Member AMS of Ukraine O.V. Stefanova. K., 2001 .-- C 379-385.
  9. Ershov F.I. Kiselev O.K. Interferons and their inducers (from molecules to drugs). M.: GOETAR-Media, 2005 .-- 368 p.
  11. Spivak N.Ya., Belotsky SM. Interferon from a molecule to a drug . Fiziol. journal 2007. 53, No. 2. FROM. 98-104.
  13. Shai D.S., Zholobak N.M., Lyakhov S.A., Maltsev G.V., Fernandez de Rivas CO., Litvinova L.O., Androna-ti S.A., Spivak M.Ya. Interferonogenic activity is analogous to amixin and lower diphenyl . Mikrobiol. journal 2007. 69, No. 5. C 59-64.
  15. Shay D.S., Zholobak N.M., Spivak M.Ya. Protiger-petical and interferonogenic of new original inductor-interferon analogue of amixin . Immunology and allergology. 2007. No. 2. C 74.
  17. Shay D.S., Zholobak N.M., Spivak M.Ya. Stan sistemi Interferonu in mishy, ​​dubbed amiksinom thoy analogs . There it is. 2007.-N 1. C 22 23.
  19. Bogorad-Kobelska O.S., Zholobak N.M., Dolga O.V., Maltzev G.M., Lyakhov S.A., Andronati S.A., Spivak M.Ya. Diphenyl derivatives: cytotoxicity, antiviral and IFN-inducing activities in vitro . Intern. J. Biomedic. 2011. 1,N 3. P. 153-157.
  21. Bredehorn T., Duncker G.I. Tilorone-induced func­tional changes in the rat retina . Klin. Monbl. Augenheilkd. 2000. 216, N 4. P. 219-222. CrossRef PubMed
  23. Cavallini G., Massarani E. The concept of a support­ing moiety as applied to the synthesis of anti-viral compounds . J. Med. and Pharm. Chem. 1959. 1, N 4. P. 365-370. CrossRef PubMed
  25. Danve-Szatanek C, Aymard M., Thouvenot D., Morfin F., Agius G., Bertin I., Billaudel S., Chanzy B., Coste-Burel M., Finkielsztejn L., Fleury H., Hadou T., Henquell C, Lafeuille H., Lafon M.E., Le Faou A., Legrand M.C, Maille L., Mengelle C, Morand P., Morinet F., Nicand E., Omar S., Picard B., Pozzetto B., Puel J., Raoult D., ScieuxC, Segondy M., Seigneurin J.M., Teyssou R., Zandotti C. Surveillance network for herpes simplex virus resistance to antivi­ral drugs: 3-year follow-up . J. Clin. Microbiol. 2004. 42. P. 242-249. CrossRef PubMed PubMedCentral
  27. Delogu I., Pastorino B., Baronti C, Nougairde A., Bon­net E., de Lamballerie X. In vitro antiviral activity of arbidol against Chikungunya virus and characteristics of a selected resistant mutant . Antivir. Res. 2011. 90, N 3. P. 99 107. CrossRef PubMed
  29. Fischer J., Lullmann H., Lullmann-Rauch R. Drug-induced lysosomal storage of sulphated glycosaminoglycans . Gen. Pharmacol: Vasc. Syst. 1996. 27,N 8. P. 1317-1324. CrossRef  
  30. He G., Qiao J., Dong C, He C, Zhao L., Tian Y. Amantadine-resistance among H5N1 avian influenza viruses isolated in Northern China . Antivir. Res. 2008. 77, N 1. P. 72-76. CrossRef PubMed
  32. Katz E., Margalith E., Winer B. Inhibition of herpes virus deoxyribonucleic acid and protein synthesis by tilorone hydrochloride . Antimicrob. Agents Chemo­ther. 1976. 9, N 1. P. 189-195. CrossRef PubMed PubMedCentral
  34. Malvy D., Treilhaud M., Bouee S., Crochard A., Vallee D., Hasnaoui A.E., Aymard M. and the RESSAC Study Group. A retrospective, case-control study of acyclovirresistance in herpes simplex virus . Clin. Infect. Dis. 2005. 41. P. 320-326. CrossRef PubMed
  36. Medvedev A.E., Fuchs B.B., Rankhmilevich A.L. A study of the action of immunosuppressive factors from tumour cells on lymphocytes and macrophages in vitro and on the graft-versus-host reaction in mice . Biomed. Sci. 1990. N 1. P. 261-266.
  38. Morahan P.S., Munson J.A, Baird L.G., Kaplan A.M., Regelson W. Antitumor action of pyran copolymer and tilorone against Lewis lung carcinoma and B-16 melanoma . Cancer Res. 1974. 34. P. 506-511.
  40. Pestka S. The interferons: 50 years after their discovery, there is much more to learn . J. Biol. Chem. 2007. 282, N 28. P. 20047-20051. CrossRef PubMed
  42. Prokopek M. The tilorone-induced mucopolysaccha­ridosis in rats: Biochemical investigations . Biochem. Pharmacol. 1991. 42, N 11. P. 2187-2191. CrossRef  
  43. Safrin S., Crumpacker C, Chatis P., Davis R., Hafner R., Rush J., Kessler H.A., Landry B., Mills J., and other members of the AIDS Clinical Trials Group. A controlled trial comparing foscarnet with vidarabine for acyclovir-resistant mucocutaneous herpes simplex in the acquired immunodeficiency syndrome . N. Engl. J. Med. 1991. 325, N 8. P. 551-555. CrossRef PubMed

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