In Vitro and in Vivo Antischistosomal Activities of Chalcones

Chem Biodivers. 2018 Dec;15(12):e1800398. doi: 10.1002/cbdv.201800398. Epub 2018 Dec 10.

Abstract

In this study, we evaluated the in vitro and in vivo schistosomicidal activities of chalcones against Schistosoma mansoni worms. In vitro assays revealed that chalcones 1 and 3 were the most active compounds, without affecting significantly mammalian cells. Confocal laser scanning microscopy and scanning electron microscopy studies revealed reduction on the numbers of tubercles and morphological alterations in the tegument of S. mansoni worms after in vitro incubation with chalcones 1 and 3. In a mouse model of schistosomiasis, the oral treatment (400 mg/kg) with chalcone 1 or 3 significantly caused a total worm burden reduction in mice. Chalcone 1 showed significant inhibition of the S. mansoni ATP diphosphohydrolase activity, which was corroborated by molecular docking studies. The results suggested that chalcones could be explored as lead compounds with antischistosomal properties.

Keywords: Schistosoma mansoni ATP diphosphohydrolase; biological activity; chalcones; cytotoxicity; natural products; schistosomiasis.

MeSH terms

  • Administration, Oral
  • Animals
  • Anthelmintics / chemical synthesis
  • Anthelmintics / chemistry*
  • Anthelmintics / pharmacology
  • Anthelmintics / therapeutic use
  • Apyrase / antagonists & inhibitors
  • Apyrase / metabolism
  • Binding Sites
  • Chalcones / chemical synthesis
  • Chalcones / chemistry
  • Chalcones / pharmacology*
  • Chalcones / therapeutic use
  • Disease Models, Animal
  • Helminth Proteins / antagonists & inhibitors
  • Helminth Proteins / metabolism
  • Mice
  • Microscopy, Confocal
  • Microscopy, Electron, Scanning
  • Molecular Docking Simulation
  • Protein Structure, Tertiary
  • Schistosoma mansoni / drug effects*
  • Schistosoma mansoni / enzymology
  • Schistosomiasis mansoni / drug therapy
  • Schistosomiasis mansoni / pathology
  • Structure-Activity Relationship

Substances

  • Anthelmintics
  • Chalcones
  • Helminth Proteins
  • Apyrase