In vitro activity of the interaction between taxifolin (dihydroquercetin) and pyrimethamine against Toxoplasma gondii

Chem Biol Drug Des. 2018 Jan;91(1):194-201. doi: 10.1111/cbdd.13070. Epub 2017 Aug 11.

Abstract

Toxoplasmosis is one of the most neglected zoonotic foodborne parasitic diseases that cause public health and socioeconomic concern worldwide. The current drugs used for the treatment of toxoplasmosis have been identified to have clinical limitations. Hence, new drugs are urgently needed to eradicate T.gondii infections globally. Here, an in vitro anti-Toxoplasma gondii activity of taxifolin (dihydroquercetin) and dihydrofolate inhibitor (pyrimethamine) alone and in combination with a fixed concentration of pyrimethamine were investigated against the rapidly proliferating T.gondii RH strain at 48 hr using colorimetric assay. Pyrimethamine showed the highest anti-T. gondii activity with IC50P of 0.84 μg/ml (p > .05), respectively. The combination of pyrimethamine with dihydroquercetin gave a significant inhibitory activity against tachyzoites in in vitro with IC50p of 1.39 μg/ml (p < .05). The IC50p ranges obtained for the individual and the combination of taxifolin with pyrimethamine inhibition of parasite growth were not cytotoxic to the infected HFF and Hek-293 cell lines used. These compounds combination should be investigated further using in vivo model of toxoplasmosis.

Keywords: combination; drug; flavonoid; therapy; toxoplasmosis.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Antiparasitic Agents / chemistry
  • Antiparasitic Agents / pharmacology*
  • Antiparasitic Agents / therapeutic use
  • Cell Survival / drug effects
  • Drug Synergism
  • HEK293 Cells
  • Humans
  • Inhibitory Concentration 50
  • Mice
  • Pyrimethamine / chemistry*
  • Pyrimethamine / pharmacology
  • Pyrimethamine / therapeutic use
  • Quercetin / analogs & derivatives*
  • Quercetin / chemistry
  • Quercetin / pharmacology
  • Quercetin / therapeutic use
  • Toxoplasma / drug effects*
  • Toxoplasmosis, Animal / drug therapy
  • Toxoplasmosis, Animal / pathology

Substances

  • Antiparasitic Agents
  • Quercetin
  • taxifolin
  • Pyrimethamine