Anti-Adenoviral Activity of 2-(3-Chlorotetrahydrofuran-2-yl)-4-Tosyl-5-(Perfluoropropyl)-1,2,3-Triazole

Medicina (Kaunas). 2018 Nov 5;54(5):81. doi: 10.3390/medicina54050081.

Abstract

Background and objectives: A considerable increase in the levels of adenoviral diseases among both adults and children necessitate the development of effective methods for its prevention and treatment. The synthesis of the new fluorinated 1,2,3-triazoles, and the study of the mechanisms of their action, are promising for the development of efficient antiviral drugs of our time. Materials and Methods: Antiviral activity and cell cytotoxic effect of 2-(3-chlorotetrahydrofuran-2-yl)-4-tosyl-5-(perfluoropropyl)-1,2,3-triazole (G29) were determined by MTT (3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyl tetrazolium bromide) assay. The influence of the compound on the infectivity of human adenovirus type 5 (HAdV-5) was carried out via the cytomorphology method. The influence of the compound on the cell cycle under a condition of adenovirus infection was studied using flow cytometric analysis of propidium iodide-stained cells. Results: It was found that G29 suppressed HAdV-5 reproduction by 50% in concentrations of 37 μg/mL. Furthermore, the compound reduced the titer of virus obtained de novo, and inhibited HAdV-5 inclusion bodies formation by 84⁻90%. The use of fluorinated compounds under the conditions of adenovirus infection decreased the number of apoptotic cells by 11% and the number of cells in S phase by 21⁻42% compared to the profile of infected cells. Conclusions: The fluorinated compound G29 showed moderate activity against HAdV-5 based on several mechanisms. It led to the normalization of the life cycle of cells infected with adenovirus to the level of non-infected cells and caused the obstruction of HAdV-5 reproduction, inducing the formation of non-infectious virus progeny.

Keywords: 1,2,3-triazole; antiviral activity; cell cycle; human adenovirus; protein kinase.

MeSH terms

  • Adenovirus Infections, Human / drug therapy
  • Adenovirus Infections, Human / prevention & control
  • Adenoviruses, Human / drug effects*
  • Animals
  • Antiviral Agents / chemical synthesis*
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Antiviral Agents / therapeutic use
  • Casein Kinase II / antagonists & inhibitors
  • Cattle
  • Cell Cycle / drug effects
  • Cell Line
  • Cell Survival / drug effects
  • Fluorine Compounds / chemical synthesis*
  • Fluorine Compounds / chemistry
  • Fluorine Compounds / pharmacology*
  • Fluorine Compounds / therapeutic use
  • Microscopy, Fluorescence
  • Molecular Mimicry
  • Triazoles / chemical synthesis*
  • Triazoles / chemistry
  • Triazoles / pharmacology*
  • Triazoles / therapeutic use
  • Virus Replication / drug effects

Substances

  • Antiviral Agents
  • Fluorine Compounds
  • Triazoles
  • Casein Kinase II