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In vitro and in vivo evaluation of six artemisinin derivatives against Schistosoma mansoni

  • Sheila de A. P. Corrêa
  • Rosimeire N. de Oliveira
  • Tiago M. F. Mendes
  • Karina Rodrigues dos Santos
  • Sinésio Boaventura Jr.
  • Vera Lúcia Garcia
  • Verónica de L. S. Jeraldo
  • Silmara M. AllegrettiEmail author
Helminthology - Original Paper
  • 47 Downloads

Abstract

Schistosomiasis is a tropical neglected disease whose socioeconomic impact is surpassed only by malaria. Until recently, praziquantel (PZQ) has been the only available drug, raising concerns that tolerant/resistant strains may appear. Since the discovery of the schistosomicidal potential of artemisinin (ART), new derivatives have been produced and evaluated. In this work, we evaluated the activity of ART derivatives against Schistosoma mansoni, both in vitro and in vivo. In the in vitro assay, worm survival, oviposition, and morphological alterations were evaluated. Further analysis of morphological alterations and membrane integrity was conducted using scanning electron microscopy and a cell-permeable, benzimidazole dye (Hoescht 33258) that binds to the minor groove of double stranded DNA. For the in vivo assay, artesunic acid (AcART) and dihydroartemisinin acetate (AcDQHS) were selected, since they showed the best in vitro results. Infected mice treated 21, 45, or 60 days post-infection (dpi), with a concentration of 100 mg/kg of either AcART or AcDQHS, showed a significant worm reduction (particularly in females), fewer eggs eliminated in feces, and a decrease of immature eggs in the intestinal tissues. Our results indicate that AcART and AcDQHS have some schistosomicidal activity against juvenile and adult stages of S. mansoni.

Keywords

Schistosoma mansoni Artemisinin derivatives Artesunic acid Dihydroartemisinin acetate 

Notes

Acknowledgments

The authors thank the Coordenação de Aperfeiçoamento de Pessoal de Nível Superior (CAPES) for their support, Finance Code 001. The authors also thank Dr. Paul Ormond for revising the manuscript.

Compliance with ethical standards

Conflict of interest

The authors confirm that there are no known conflicts of interest associated with this publication and there has been no financial support for this work that could have influenced its outcome.

Supplementary material

436_2018_6188_Fig6_ESM.png (204 kb)
Figure S1

Cytotoxic analysis. Growth curves of non-tumor (HaCaT) and tumor (U251; MCF-7; NCI-ADR/RES; 786-0; NCI-H460; PC-3; OVCAR-03; HT29; K562) cell lines after exposure for 48 h to different concentrations of A) doxorubicin (reference drug), B) artesunic acid and C) dihydroartemisinin acetate. (PNG 203 kb)

436_2018_6188_MOESM1_ESM.tif (258 kb)
High-resolution image (TIF 257 kb)

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Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Sheila de A. P. Corrêa
    • 1
  • Rosimeire N. de Oliveira
    • 1
  • Tiago M. F. Mendes
    • 1
  • Karina Rodrigues dos Santos
    • 1
  • Sinésio Boaventura Jr.
    • 2
  • Vera Lúcia Garcia
    • 2
  • Verónica de L. S. Jeraldo
    • 3
  • Silmara M. Allegretti
    • 1
    Email author
  1. 1.Animal Biology Department, Biology InstituteCampinas State University (UNICAMP)CampinasBrazil
  2. 2.Multidisciplinary Center of Chemical Biological and Agricultural Research (CPQBA)Campinas State University (UNICAMP)PaulíniaBrazil
  3. 3.ITP, Infectious and Parasitic Diseases LaboratoryInstitute of Technology and ResearchAracajuBrazil

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