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Halogenated Ribofuranosylbenzimidazoles

  • Chapter
Antiviral Drugs and Interferon: The Molecular Basis of Their Activity

Part of the book series: Developments in Molecular Virology ((DMVI,volume 4))

Abstract

Halogenated ribofuranosylbenzimidazoles are the only known reversible and selective inhibitors of transcription of cellular or viral RNA by RNA polymerase II. The reversible inhibition of mRNA synthesis in eukaryotic cells is biologically the most important consequence of the novel action of these compounds. In different systems, 5,6-dichloro-1-β-D-ribofuranosylbenzimidazole (DRB) (Fig. 1) blocks initiation or causes premature termination of transcripts synthesized by RNA polymerase II. Although DRB inhibits essentially completely the synthesis of most mRNAs, the synthesis of certain viral and cellular mRNAs is resistant. Indeed, 20–30% of the total cellular heterogeneous nuclear RNA (hnRNA) synthesis is resistant to inhibition by DRB even at very high concentrations. DRB itself, and not a phosphorylated derivative of DRB, inhibits RNA synthesis in eukaryotic cells. The ribofuranose moiety in the β configuration is essential for selective activity, which requires a free 3′ hydroxyl group. Activity of 1-β-D-ribofuranosylbenzimidazoles increases with multiple substitution of halogen atoms in the benzenoid ring. The most active derivatives inhibit RNA synthesis in the 1–2 µM concentration range.

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  1. The Rockefeller University New York, New York, 10021, USA

    Igor Tamm, Robert A. Lamb & Allan R. Goldberg

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  1. Igor Tamm
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  2. Pravinkumar B. Sehgal
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  1. The Hebrew University of Jerusalem, Israel

    Yechiel Becker

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Tamm, I., Sehgal, P.B., Lamb, R.A., Goldberg, A.R. (1984). Halogenated Ribofuranosylbenzimidazoles. In: Becker, Y., Hadar, J. (eds) Antiviral Drugs and Interferon: The Molecular Basis of Their Activity. Developments in Molecular Virology, vol 4. Springer, Boston, MA. https://doi.org/10.1007/978-1-4613-3804-8_14

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