[AntiEBV activity of 6-azacytidine and its derivatives]

Mikrobiol Z. 2011 Nov-Dec;73(6):41-9.
[Article in Russian]

Abstract

Epstein-Barr virus (EBV) causes several lymphoproliferative diseases, lesions of the central and peripheral nervous systems. Spectrum of etiotropic medicines against EBV is limited. The paper presents the anti-virus research of modified nucleoside with a wide spectrum of action - 6-azacytidine and its derivatives (2'-3'-seco-5-methyl-6-AC, 2',3'-dideoxy-2',3'-didehydro-6-AC and 2'-deoxy-6-AC) on the model of Epstein-Barr virus in Raji lymphoblastoid cells. Parameters of cytotoxicity (CC,) for the investigated substances were determined which amounted to 120 microg/ml, 180 microg/ml, 500 microg/ml, 330 microg/ml, and the effective concentration (ECU)--0.5 microg/ml. 1 microg/ml, 4 microg/ml, 11 microg/ml, in accordance with the sequence of preparations listed above. The results indicate a high antiEBV activity since their selectivity indexes (SI) were 240, 180, 125, 30 that is 1.3-10 times higher than the reference substance acycloguanosine. Apoptosis-stimulating action of 6-azacytidine and its derivatives was revealed. An increase of percentage of apoptotic cells in EBV-infected Raji cells and those treated with investigated substances as compared to uninfected ones was observed after 24 hours. Thus, our results provide new biological properties of the azacytidine substances.

MeSH terms

  • Acyclovir / pharmacology
  • Apoptosis / drug effects*
  • Azacitidine / analogs & derivatives*
  • Azacitidine / chemistry
  • Azacitidine / pharmacology
  • B-Lymphocytes / drug effects*
  • B-Lymphocytes / pathology
  • B-Lymphocytes / virology
  • Burkitt Lymphoma / complications
  • Burkitt Lymphoma / drug therapy*
  • Burkitt Lymphoma / pathology
  • Burkitt Lymphoma / virology
  • Cell Survival / drug effects
  • Cells, Cultured
  • DNA, Viral / analysis
  • DNA, Viral / biosynthesis
  • Epstein-Barr Virus Infections / complications
  • Epstein-Barr Virus Infections / drug therapy*
  • Epstein-Barr Virus Infections / pathology
  • Epstein-Barr Virus Infections / virology
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / growth & development
  • Humans
  • Inhibitory Concentration 50
  • Polymerase Chain Reaction
  • Viral Load / drug effects
  • Virus Replication / drug effects

Substances

  • DNA, Viral
  • Azacitidine
  • Acyclovir
  • 6-azacytidine