Synthesis and in-vitro evaluation of 2-amino-4-arylthiazole as inhibitor of 3D polymerase against foot-and-mouth disease (FMD)

Eur J Med Chem. 2015 Sep 18:102:387-97. doi: 10.1016/j.ejmech.2015.08.020. Epub 2015 Aug 12.

Abstract

Foot-and-mouth disease (FMD) is a highly contagious vesicular disease of livestock caused by a highly variable RNA virus, foot-and-mouth disease virus (FMDV). One of the targets to suppress expansion of and to control FMD is 3D polymerase (FMDV 3Dpol). In this study, 2-amino-4-arylthiazole derivatives were synthesized and evaluated for their inhibitory activity against FMDV 3Dpol. Among them, compound 20i exhibited the most potent functional inhibition (IC50 = 0.39 μM) of FMDV 3D polymerase and compound 24a (EC50 = 13.09 μM) showed more potent antiviral activity than ribavirin (EC50 = 1367 μM) and T1105 (EC50 = 347 μM) with IBRS-2 cells infected by the FMDV O/SKR/2010 strain.

Keywords: 2-Amino-4-arylthiazole; 3D polymerase (3Dpol); Antiviral; Foot-and-mouth disease virus (FMDV); Inhibitor.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antigens, Viral / metabolism
  • Antiviral Agents / chemical synthesis
  • Antiviral Agents / chemistry
  • Antiviral Agents / pharmacology*
  • Cell Line
  • Cell Survival / drug effects
  • Dose-Response Relationship, Drug
  • Enzyme Inhibitors / chemical synthesis
  • Enzyme Inhibitors / chemistry
  • Enzyme Inhibitors / pharmacology*
  • Foot-and-Mouth Disease / drug therapy*
  • Foot-and-Mouth Disease / metabolism
  • Foot-and-Mouth Disease Virus / drug effects*
  • Foot-and-Mouth Disease Virus / enzymology
  • Molecular Structure
  • Structure-Activity Relationship
  • Swine
  • Viral Nonstructural Proteins / antagonists & inhibitors*
  • Viral Nonstructural Proteins / metabolism

Substances

  • Antigens, Viral
  • Antiviral Agents
  • Enzyme Inhibitors
  • Viral Nonstructural Proteins
  • virus-infection-associated antigen, Foot-and-mouth disease virus