Biopolym. Cell. 1996; 12(2):74-83.
Viruses and Cell
Aromatic thiosemicarbazones, their antiviral action and interferon. 1. The decreasing of adenovirus type 1 resistance against interferon by methisazone in vitro
1Patskovsky Yu. V., 1Negrebetskaya E. N., 2Chernomaz A. A., 1Voloshchuk T. P., 1Rubashevsky E. L., 1Kitam O. E., 1Tereshchenko M. I., 2Nosach L. N., 1Potopalsky A. I.
  1. Institute of Molecular Biology and Genetics, NAS of Ukraine
    150, Akademika Zabolotnoho Str., Kyiv, Ukraine, 03680
  2. D. K. Zabolotny Institute of Microbiology and Virology, NAS of Ukraine
    154, Academika Zabolotnogo Str., Kyiv, Ukraine, 03680


The mechanism of N-mvthyl-izatin-thiocarbazone (methisazone, MelBT) antiviral activity has been studied on Ad 1-infected HEp2 and HeLa cells. MelBT did not induce interferon and did not directly inhibit viraland cell translation. The adenoviral infection was not affected by recombinani human interferon a2 (rlFN). MelBT showed antiviral effect in Adl-infected HEp2 or HeLa cells when rlFN had added to HeLa cells or in the period of interferon induction during virus infection (in HEp2 cells). In the presence of this compound, the ElA transcription was unchanged in infected cells as compared to untreated control, while early transcription was decreased, the beginning of viral replication being retarded. Futhermore, the VA1 RNA synthesis was also greatly suppressed. These effects were independent on interferon treatment and disappeared when MelBT had been added during the late phase of virus growth cycle. ctually, MelBT can induce the delay of VA1 RNA transcription promoting interferon antiviral effect.


[1] Bauer DJ. Clinical experience with the antiviral drug marboran (1-methylisatin 3-thiosemicarbazone). Ann N Y Acad Sci. 1965;130(1):110-7.
[2] Potopal'skiy AI, Lozyuk LV, Mirolyubova AN, Besarabov BF. Antiviral, anticancer and antileukemia drug izatizon. Kiev: Naukova Dumka, 1991. 192 p.
[3] Magee WE, Bach MK. Biochemical studies on the antiviral activities of the isatin-beta-thiosemicarbazones. Ann N Y Acad Sci. 1965;130(1):80-91.
[4] Appleyard G, Hume VB, Westwood JC. The effect of thiosemicarbazones on the growth of rabbit pox virus in tissue culture. Ann N Y Acad Sci. 1965;130(1):92-104.
[5] Pennington TH. Isatin-beta-thiosemicarbazone causes premature cessation of vaccinia virus-induced late post-replicative polypeptide synthesis. J Gen Virol. 1977;35(3):567-71.
[6] Prusoff WH, Goz B. Potential mechanisms of action of antiviral agents. Fed Proc. 1973;32(6):1679-87.
[7] Woodson B, Joklik WK. The inhibition of vaccinia virus multiplication by isatin-beta-thiosemicarbazone. Proc Natl Acad Sci U S A. 1965;54(3):946-53.
[8] Cooper JA, Moss B, Katz E. Inhibition of vaccinia virus late protein synthesis by isatin-beta-thiosemicarbazone: characterization and in vitro translation of viral mRNA. Virology. 1979;96(2):381-92.
[9] Levinson W. Inhibition of viruses, tumors and pathogenic microorganisms by izatin-thiosemicarbazone and other thiose micarbazones. Selective inhibitors of viral functions. Ed. W. A. Carter. London: CRC press, 1973: 213-26.
[10] Bauer DJ, Apostolov K. Adenovirus multiplication: inhibition by methisazone. Science. 1966;154(3750):796-7.
[11] Katz E, Margalith E, Winer B. The effect of isatin beta thiosemicarbazone (IBT)-related compounds on IBT-resistant and on IBT-dependent mutants of vaccinia virus. J Gen Virol. 1974;25(2):239-44.
[12] Robinson AJ, Younghusband HB, Bellett AJ. A circula DNA-protein complex from adenoviruses. Virology. 1973;56(1):54-69.
[13] Anderson CW, Lewis JB, Atkins JF, Gesteland RF. Cell-free synthesis of adenovirus 2 proteins programmed by fractionated messenger RNA: a comparison of polypeptide products and messenger RNA lengths. Proc Natl Acad Sci U S A. 1974;71(7):2756-60.
[14] O'Malley RP, Mariano TM, Siekierka J, Mathews MB. A mechanism for the control of protein synthesis by adenovirus VA RNAI. Cell. 1986;44(3):391-400.
[15] Maniatis T, Fritsch EF, Sambrook J. Molecular cloning: a laboratory manual. New York: Cold Spring Harbor Lab, 1982; 545 p.
[16] Weinmann R, Raskas HJ, Roeder RG. Role of DNA-dependent RNA polymerases II and III in transcription of the adenovirus genome late in productive infection. Proc Natl Acad Sci U S A. 1974;71(9):3426-39.
[17] Rice AP, Kerr IM. Interferon-mediated, double-stranded RNA-dependent protein kinase is inhibited in extracts from vaccinia virus-infected cells. J Virol. 1984;50(1):229-36.
[18] D'Halluin JC, Leclere V. The adenovirus El A gene: immortalizating nuclear oncogene prototype. Bull Inst Pasteur. 1992; 90(1): 45-65.
[19] Culp JS, Webster LC, Friedman DJ, Smith CL, Huang WJ, Wu FY, Rosenberg M, Ricciardi RP. The 289-amino acid E1A protein of adenovirus binds zinc in a region that is important for trans-activation. Proc Natl Acad Sci U S A. 1988;85(17):6450-4.
[20] Sadler PW. Antiviral chemotherapy with isatin-beta-thiosemicarbazone and its derivatives. Ann N Y Acad Sci. 1965;130(1):71-9.