Lumefantrine and o-choline - Parasite metabolism specific drug molecules inhibited in vitro growth of Theileria equi and Babesia caballi in MASP culture system

Ticks Tick Borne Dis. 2019 Apr;10(3):568-574. doi: 10.1016/j.ttbdis.2019.01.004. Epub 2019 Jan 21.

Abstract

Theileria equi and Babesia caballi are tick-borne apicomplexan haemoprotozoan parasites of equines and are responsible for considerable economic losses to stakeholders. Chemotherapeutic drugs that are available not only require multiple dosages but also prompt multiple organ toxicity in treated host though incapable of clearing parasitaemia completely. In this study, we have screened the in vitro inhibitory efficacy of four different drug molecules (o-choline, DABCO®, lumefantrine and eugenol) against T. equi and B. caballi, targeting different parasite metabolism pathways. Imidocarb dipropionate and diminazene aceturate were used as reference control drugs. The 50% in vitro growth inhibitory concentration (IC50) of lumefantrine, o-choline, DABCO® and eugenol for T. equi were: 30.90 μM; 84.38 μM; 443 μM; 120 μM and for B. caballi growth inhibition were: 5.58 μM; 135.29 μM; 150 μM; 197.05 μM, respectively. Imidocarb dipropionate inhibited the in vitro growth of T. equi at IC50 of 257.5 nM, while diminazene aceturate inhibited the in vitro growth of B. caballi at IC50 of 22 nM. DABCO® and eugenol were not so effective in inhibiting the in vitro growth of T. equi and B. caballi, while lumefantrine and o-choline significantly (p ≤ 0.05) inhibited the in vitro growth of these piroplasms targeting haem digestion and parasite membrane phospholipid synthesis.

Keywords: Babesia caballi; Haem; Lumefantrine; O-choline; PBMCs viability; Phosphatidylcholine; Theileria equi.

MeSH terms

  • Animals
  • Babesia / drug effects*
  • Babesia / growth & development
  • Cell Survival / drug effects
  • Cells, Cultured
  • Choline / pharmacology*
  • Hemoglobins / metabolism
  • Horses
  • Inhibitory Concentration 50
  • Lactates / metabolism
  • Lumefantrine / pharmacology*
  • Metabolic Networks and Pathways / drug effects*
  • Phospholipids / metabolism
  • Phylogeny
  • Theileria / drug effects*
  • Theileria / growth & development

Substances

  • Hemoglobins
  • Lactates
  • Phospholipids
  • Lumefantrine
  • Choline