An updated review of chemical compounds with anti-Toxoplasma gondii activity

Eur J Med Chem. 2023 Dec 15:262:115885. doi: 10.1016/j.ejmech.2023.115885. Epub 2023 Oct 16.

Abstract

The opportunistic apicomplexan parasite Toxoplasma gondii is the etiologic agent for toxoplasmosis, which can infect a widespread range of hosts, particularly humans and warm-blooded animals. The present chemotherapy to treat or prevent toxoplasmosis is deficient and is based on diverse drugs such as atovaquone, trimethoprim, spiramycine, which are effective in acute toxoplasmosis. Therefore, a safe chemotherapy is required for toxoplasmosis considering that its responsible agent, T. gondii, provokes severe illness and death in pregnant women and immunodeficient patients. A certain disadvantage of the available treatments is the lack of effectiveness against the tissue cyst of the parasite. A safe chemotherapy to combat toxoplasmosis should be based on the metabolic differences between the parasite and the mammalian host. This article covers different relevant molecular targets to combat this disease including the isoprenoid pathway (farnesyl diphosphate synthase, squalene synthase), dihydrofolate reductase, calcium-dependent protein kinases, histone deacetylase, mitochondrial electron transport chain, etc.

Keywords: Calcium-dependent protein kinases; Dihydrofolate reductase; Farnesyl diphosphate synthase; Mitochondrial electron transport chain; Squalene synthase; Toxoplasma gondii; Toxoplasma gondii adenosine kinase; Toxoplasmosis.

Publication types

  • Review

MeSH terms

  • Animals
  • Atovaquone / metabolism
  • Atovaquone / pharmacology
  • Atovaquone / therapeutic use
  • Female
  • Humans
  • Mammals
  • Pregnancy
  • Toxoplasma*
  • Toxoplasmosis* / drug therapy
  • Trimethoprim / pharmacology

Substances

  • Atovaquone
  • Trimethoprim