In vitro and in vivo antischistosomal activity of ferroquine derivatives

Particle and Fibre Toxicology

Christophe Biot²  Gilles Gasser¹  Riccardo Rubbiani¹  Mireille Vargas³  Jennifer Keiser³ 

[1] Department of Chemistry, University of Zurich, Winterthurerstrasse 190, CH-8057 Zurich, Switzerland;CNRS, UMR 8576, F-59650 Villeneuve d’Ascq, France;University of Basel, Basel, Switzerland

关键词: In vivo;    In vitro;    Hydroxyl-ferroquine;    Ruthenoquine;    Chloroquine;    Ferroquine;    Schistosoma mansoni;   

Others  :  1150400
DOI  :  10.1186/1756-3305-7-424

 received in 2014-08-22, accepted in 2014-08-27,  发布年份 2014

【 摘 要 】

Background

Schistosomiasis is a neglected tropical disease and drug-repurposing is a useful strategy to fill its exhausted drug development pipeline. The ferrocenyl analogue of chloroquine, ferroquine, is an antimalarial in late-stage drug development. The aim of the present work was to study the antischistosomal activity of ferroquine against Schistosoma mansoni adult worms and newly transformed schistosomula (NTS) in vitro and in vivo. Hydroxyl-ferroquine and ruthenoquine were included to study the potential role of reactive oxygen species in the antischistosomal activity. Chloroquine and mefloquine, the later described for its antischistosomal properties, served as comparators.

Findings

All metal complexes were shown to be moderately cytotoxic on human cervix HeLa cancer cells and human fetal lung fibroblasts MRC-5. 72 hours post-incubation NTS exposed to 33.3 µM ruthenoquine had died, while ferroquine and hydroxyl-ferroquine treated worms were strongly affected. No activity was observed treating NTS with chloroquine at 33.3 µM. Incubation of adult S. mansoni with 33.3 µM of the organometallic derivatives were highly affected in viability but were still alive 72 hours post-incubation. Mefloquine showed the highest activity against NTS and adult S. mansoni. Low total worm burden reductions of 0-36% were observed following oral administration of 200–800 mg/kg of the ferroquine derivatives to S. mansoni-infected mice.

Conclusions

The organometallic compounds evaluated in this study revealed moderate in vitro activity against both larval and adult stages of S. mansoni but low in vivo activity. No correlation can be drawn between the antimalarial and antischistosomal activity of chloroquine analogues and oxidative shock does not seem to play a role in the activity of these compounds against S. mansoni.

【 授权许可】

   
2014 Keiser et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

Figure 2.

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