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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

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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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