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Antiparasitic properties of cardiovascular agents against human intravascular parasite schistosoma mansoni

  • Raquel Porto
  • , Ana C. Mengarda
  • , Rayssa A. Cajas
  • , Maria C. Salvadori
  • , Fernanda S. Teixeira
  • , Daniel D.R. Arcanjo
  • , Abolghasem Siyadatpanah
  • , Maria de Lourdes Pereira
  • , Polrat Wilairatana
  • , Josué de Moraes
  • Guarulhos University
  • University of São Paulo
  • Federal University of Piaui
  • Birjand University of Medical Sciences
  • University of Aveiro

Research output: Contribution to journalArticlepeer-review

29 Citations (Scopus)

Abstract

The intravascular parasitic worm Schistosoma mansoni is a causative agent of schistosomiasis, a disease of great global public health significance. Praziquantel is the only drug available to treat schistosomiasis and there is an urgent demand for new anthelmintic agents. Adopting a phenotypic drug screening strategy, here, we evaluated the antiparasitic properties of 46 commercially available cardiovascular drugs against S. mansoni. From these screenings, we found that amiodarone, telmisartan, propafenone, methyldopa, and doxazosin affected the viability of schistosomes in vitro, with effective concentrations of 50% (EC50) and 90% (EC90) values ranging from 8 to 50 µM. These results were further supported by scanning electron microscopy analysis. Subsequently, the most effective drug (amiodarone) was further tested in a murine model of schistosomiasis for both early and chronic S. mansoni infections using a single oral dose of 400 mg/kg or 100 mg/kg daily for five consecutive days. Amiodarone had a low efficacy in chronic infection, with the worm and egg burden reduction ranging from 10 to 30%. In contrast, amiodarone caused a significant reduction in worm and egg burden in early infection (>50%). Comparatively, treatment with amiodarone is more effective in early infection than praziquantel, demonstrating the potential role of this cardiovascular drug as an antischistosomal agent.

Original languageEnglish
Article number686
JournalPharmaceuticals
Volume14
Issue number7
DOIs
Publication statusPublished - Jul 2021

Keywords

  • Amiodarone
  • Anthelmintic
  • Antiarrhythmic
  • Antiparasitic
  • Antischistosomal
  • Cardiovascular agents
  • Drug repurposing
  • Schistosomiasis

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