Virtual screening, synthesis and biological evaluation of DNA intercalating antiviral agents

Bioorg Med Chem Lett. 2017 Aug 15;27(16):3915-3919. doi: 10.1016/j.bmcl.2017.06.035. Epub 2017 Jun 13.

Abstract

This paper describes computer-aided design of new anti-viral agents against Vaccinia virus (VACV) potentially acting as nucleic acid intercalators. Earlier obtained experimental data for DNA intercalation affinities and activities against Vesicular stomatitis virus (VSV) have been used to build, respectively, pharmacophore and QSAR models. These models were used for virtual screening of a database of 245 molecules generated around typical scaffolds of known DNA intercalators. This resulted in 12 hits which then were synthesized and tested for antiviral activity against VaV together with 43 compounds earlier studied against VSV. Two compounds displaying high antiviral activity against VaV and low cytotoxicity were selected for further antiviral activity investigations.

Keywords: Antiviral activity; DNA affinity; Structure-activity modeling; Vaccinia virus; Virtual screening.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • DNA / drug effects*
  • Dose-Response Relationship, Drug
  • Drug Evaluation, Preclinical
  • Humans
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quantitative Structure-Activity Relationship
  • Vesicular stomatitis Indiana virus / drug effects*

Substances

  • Antiviral Agents
  • DNA