Identification and evaluation of 4-anilinoquin(az)olines as potent inhibitors of both dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV)

Bioorg Med Chem Lett. 2021 Nov 15:52:128407. doi: 10.1016/j.bmcl.2021.128407. Epub 2021 Oct 5.

Abstract

There is an urgent need for novel strategies for the treatment of emerging arthropod-borne viral infections, including those caused by dengue virus (DENV) and Venezuelan equine encephalitis virus (VEEV). We prepared and screened focused libraries of 4-anilinoquinolines and 4-anilinoquinazolines for antiviral activity and identified three potent compounds. N-(2,5-dimethoxyphenyl)-6-(trifluoromethyl)quinolin-4-amine (10) inhibited DENV infection with an EC50 = 0.25 µM, N-(3,4-dichlorophenyl)-6-(trifluoromethyl)quinolin-4-amine (27) inhibited VEEV with an EC50 = 0.50 µM, while N-(3-ethynyl-4-fluorophenyl)-6,7-dimethoxyquinazolin-4-amine (54) inhibited VEEV with an EC50 = 0.60 µM. These series of compounds demonstrated nearly no toxicity with CC50 values greater than 10 µM in all cases. These promising results provide a future prospective to develop a clinical compound against these emerging viral threats.

Keywords: Alphavirus; Antiviral; Dengue virus; Flavivirus; Venezuelan equine encephalitis virus.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemical synthesis
  • Aniline Compounds / chemistry
  • Aniline Compounds / pharmacology*
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Dengue Virus / drug effects*
  • Dose-Response Relationship, Drug
  • Encephalitis Virus, Venezuelan Equine / drug effects*
  • Microbial Sensitivity Tests
  • Molecular Structure
  • Quinazolines / chemical synthesis
  • Quinazolines / chemistry
  • Quinazolines / pharmacology*
  • Structure-Activity Relationship

Substances

  • Aniline Compounds
  • Antiviral Agents
  • Quinazolines
  • anilinoquinazoline