[Effect of isonicotinic acid derivates on reproduction of Epstein-Barr virus]

Mikrobiol Z. 2011 Mar-Apr;73(2):65-72.
[Article in Ukrainian]

Abstract

Current approaches to the treatment of herpes infection, particularly Epstein-Barr virus (EBV), include the use of etiotropic medicines, as well as sensitizing therapy. This virus plays an important role in the etiology of nasopharyngeal carcinoma, adenocarcinoma of the parotid glands, gastric carcinoma, Burkitt's lymphoma and lymphoproliferative syndromes [1, 2, 3]. The spectrum of drugs active against EBV remains very limited, and gancyclovir and acyclovir are used in medical practice, so the search of new compounds active against EBV remains urgent. The purpose of this work was to study antiEBV activity of isonicotinic acid derivatives in the cultures of lymphoblastoid Raji cells, B95-8, Namalwa. The indices of cytotoxicity (CC50) which amounted to 840, 1250 and 3000 microg/ml and the concentration of drugs, which inhibit the virus (IC50) reproduction is 0.1, 2.5 and 50 microg/ml, respectively, in cell cultures were identified. It was detected, the drug 4-(n-benzyl)aminocarbonyl-1-methylpyridinium iodide (PV-1) had an ability to inhibit reproduction of the Epstein-Barr virus in all studied cells cultures. The compounds PV-2 and PV-10 were less toxic in respect of the initial preparation PV-1, but their antiviral activity was manifested at 25 and 500 times higher concentrations. It, respectively, influenced the decrease of their selectivity index, which was 8400 for PV-1, 400 and 440--for PV-2 and PV-10. These studies suggest possible ways of further modification of the PV-1 molecule to create highly specific inhibitors of Epstein-Barr virus. The paper is presented in Ukrainian.

Publication types

  • English Abstract

MeSH terms

  • Animals
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Callithrix
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Cell Transformation, Viral
  • Dose-Response Relationship, Drug
  • Herpesvirus 4, Human / drug effects*
  • Herpesvirus 4, Human / physiology
  • Humans
  • Isonicotinic Acids / chemistry
  • Isonicotinic Acids / pharmacology*
  • Lymphocytes / virology
  • Molecular Structure
  • Structure-Activity Relationship
  • Virus Replication / drug effects*

Substances

  • Antiviral Agents
  • Isonicotinic Acids