Synthesis, antiamoebic and molecular docking studies of furan-thiazolidinone hybrids

Eur J Med Chem. 2016 Nov 29:124:393-406. doi: 10.1016/j.ejmech.2016.08.053. Epub 2016 Aug 25.

Abstract

In continuation of our previous work, a series of furan-thiazolidinone hybrids was prepared by Knoevenagel condensation of 3-(furan-2-ylmethyl)-2-(phenylimino)-1, 3-thiazolidin-4-one with different aryl aldehydes in presence of strong base. Some members of the series exhibited remarkable antiamoebic activity and cell viability. Three compounds (3, 6 and 11) showed excellent binding energy for Entamoeba histolytica O-acetyle-l-serine sulfohydrolase and Entamoeba histolytica thioredoxin reductase. These compounds demonstrated significant inhibition of O-acetyle-l-serine sulfohydrolase. The promising antiamoebic activity and enzymatic assay of 3, 6 and 11 make them promising molecules for further lead optimization in the development of novel antiamoebic agents.

Keywords: Antiamoebic activity; Furan; MTT assay; Thiazolidinone; Thioredoxin reductase.

MeSH terms

  • Animals
  • Antiprotozoal Agents / chemical synthesis
  • Antiprotozoal Agents / metabolism
  • Antiprotozoal Agents / pharmacokinetics
  • Antiprotozoal Agents / pharmacology
  • CHO Cells
  • Cell Survival / drug effects
  • Chemistry Techniques, Synthetic
  • Cricetinae
  • Cricetulus
  • Drug Design*
  • Entamoeba histolytica / drug effects*
  • Entamoeba histolytica / enzymology
  • Furans / chemistry*
  • Inhibitory Concentration 50
  • Molecular Docking Simulation*
  • Protein Conformation
  • Structure-Activity Relationship
  • Thiazolidines / chemical synthesis*
  • Thiazolidines / metabolism
  • Thiazolidines / pharmacokinetics
  • Thiazolidines / pharmacology*
  • Thioredoxin-Disulfide Reductase / antagonists & inhibitors
  • Thioredoxin-Disulfide Reductase / chemistry
  • Thioredoxin-Disulfide Reductase / metabolism

Substances

  • Antiprotozoal Agents
  • Furans
  • Thiazolidines
  • Thioredoxin-Disulfide Reductase
  • furan