Triazole-based compound as a candidate to develop novel medicines to treat toxoplasmosis

Katarzyna Dzitko; Agata Paneth; Tomasz Plech; Jakub Pawełczyk; Lidia Węglińska; Piotr Paneth

doi:10.1128/AAC.03832-14

Triazole-based compound as a candidate to develop novel medicines to treat toxoplasmosis

Antimicrob Agents Chemother. 2014 Dec;58(12):7583-5. doi: 10.1128/AAC.03832-14. Epub 2014 Oct 6.

Authors

Katarzyna Dzitko¹, Agata Paneth², Tomasz Plech³, Jakub Pawełczyk⁴, Lidia Węglińska³, Piotr Paneth⁵

Affiliations

¹ Department of Immunoparasitology, University of Lodz, Lodz, Poland dzika@biol.uni.lodz.pl.
² Department of Organic Chemistry, Medical University of Lublin, Lublin, Poland Institute of Applied Radiation Chemistry, Technical University of Lodz, Poland.
³ Department of Organic Chemistry, Medical University of Lublin, Lublin, Poland.
⁴ Institute for Medical Biology of the Polish Academy of Sciences, Lodz, Poland.
⁵ Institute of Applied Radiation Chemistry, Technical University of Lodz, Poland.

Abstract

This article reports anti-Toxoplasma gondii activity of 3-(thiophen-2-yl)-1,2,4-triazole-5-thione. The compound displayed significant and reproducible antiparasitic effects at nontoxic concentrations for the host cells, with an experimentally determined 50% inhibitory concentration (IC50) at least 30 times better than that of the known chemotherapeutic agent sulfadiazine. Purine nucleoside phosphorylase was defined as the probable target for anti-Toxoplasma activity of the tested compound. These results provide the foundation for future work to develop a new class of medicines to better treat toxoplasmosis.

MeSH terms

Animals
Antiprotozoal Agents / chemical synthesis
Antiprotozoal Agents / chemistry*
Antiprotozoal Agents / pharmacology
Cell Line
Dose-Response Relationship, Drug
Fibroblasts / drug effects
Fibroblasts / parasitology
HeLa Cells
Humans
Inhibitory Concentration 50
Mice
Molecular Docking Simulation
Parasitic Sensitivity Tests
Protozoan Proteins / antagonists & inhibitors*
Protozoan Proteins / chemistry
Purine-Nucleoside Phosphorylase / antagonists & inhibitors*
Purine-Nucleoside Phosphorylase / chemistry
Structure-Activity Relationship
Sulfadiazine / pharmacology
Thiophenes / chemical synthesis
Thiophenes / chemistry*
Thiophenes / pharmacology
Toxoplasma / drug effects*
Toxoplasma / enzymology
Toxoplasma / growth & development
Triazoles / chemical synthesis
Triazoles / chemistry*
Triazoles / pharmacology

Substances

3-(thiophen-2-yl)-1,2,4-triazole-5-thione
Antiprotozoal Agents
Protozoan Proteins
Thiophenes
Triazoles
Sulfadiazine
Purine-Nucleoside Phosphorylase