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5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine as inhibitors of viral and bacterial growth

Russian Journal of Bioorganic Chemistry volume 42, pages 677–684 (2016)Cite this article

Abstract

A series of 5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine have been synthesized by the interaction of 3′,5′-diacetyl-5-azidomethyl-2′-deoxyuridine with the corresponding 1-alkynes in a biphasic methylene chloride—water system catalyzed by Cu(I) followed by the deblocking with a water-alcohol ammonia solution. A low cytotoxicity of the compounds in Vero, Jurkat, and A549 cell cultures has been shown. The 2′-deoxyuridine derivatives exhibited an antiherpetic activity in vitro toward two laboratory strains of human herpes simplex virus type 1 (HSV-1): acyclovir-sensitive (HSV-1/L2) and acyclovir-resistant (HSV-1/L2RACV). They also inhibited the growth of some bacteria (Mycobacterium smegmatis, Staphylococcus aureus, Micrococcus luteus, and Leuconostoc mesenteroides) and yeasts Saccharomyces cerevisiae in vitro.

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Abbreviations

CD50 :

the concentration of a compound that causes the death of 50% of uninfected cells

CPE:

the cytopathic effect

ED50 :

the concentration of preparations that induce a 50% inhibition of the CPE

HSV-1:

human herpes simplex virus type 1

SI:

the chemotherapeutic index, which is calculated as the CD50/ED50 ratio

PFU:

plaque-forming unit

MOI:

multiplicity of infection

ACV:

acyclovir

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Authors and Affiliations

  1. Engelhardt Institute of Molecular Biology, Russian Academy of Sciences, ul. Vavilova 32, Moscow, 119991, Russia

    L. A. Alexandrova, P. N. Solyev, I. L. Karpenko & S. N. Kochetkov

  2. Gause Institute of New Antibiotics, Russian Academy of Medical Sciences, ul. Bol’shaya Pirogovskaya 11, Moscow, 119021, Russia

    O. V. Efremenkova

  3. Ivanovskii Research Institute of Virology, Gamaleya Federal Research Center for Epidemiology and Microbiology, Ministry of Public Health and Social Development of Russia, Moscow, 123098, Russia

    V. L. Andronova & G. A. Galegov

Authors
  1. L. A. Alexandrova
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  2. O. V. Efremenkova
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  3. V. L. Andronova
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  4. G. A. Galegov
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  5. P. N. Solyev
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  6. I. L. Karpenko
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  7. S. N. Kochetkov
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Correspondence to L. A. Alexandrova.

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Dedicated to the memory of the Academician A. S. Khokhlov

Original Russian Text © L.A. Alexandrova, O.V. Efremenkova, V.L. Andronova, G.A. Galegov, P.N. Solyev, I.L. Karpenko, S.N. Kochetkov, 2016, published in Bioorganicheskaya Khimiya, 2016, Vol. 42, No. 6, pp. 746–754.

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Alexandrova, L.A., Efremenkova, O.V., Andronova, V.L. et al. 5-(4-alkyl-1,2,3-triazol-1-yl)methyl derivatives of 2′-deoxyuridine as inhibitors of viral and bacterial growth. Russ J Bioorg Chem 42, 677–684 (2016). https://doi.org/10.1134/S1068162016050022

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  • DOI: https://doi.org/10.1134/S1068162016050022

Keywords

  • nucleosides
  • 1,3-dipolar cycloaddition
  • azides
  • l-alkynes
  • antibacterial activity
  • antiherpetic activity
  • cytotoxicity