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In vitro efficacy of cyclooctadepsipepdtides and aminophenylamidines alone and in combination against third-stage larvae and adult worms of Nippostrongylus brasiliensis and first-stage larvae of Trichinella spiralis

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Abstract

The present study investigates the in vitro efficacy of derivatives of the cyclooctadepsipeptides and the aminophenylamidines, which are promising candidates for the evaluation of the treatment of human soil-transmitted helminthiases. The effects of emodepside and PF1022A as well as of amidantel, deacylated amidantel and tribendimidine were evaluated in a concentration range between 0.01 and 100 μg/ml against third-stage larvae (L3) and adult worms of Nippostrongylus brasiliensis and first-stage larvae (L1) of Trichinella spiralis. Furthermore, drug combinations of PF1022A plus deacylated amidantel or tribendimidine and of tribendimidine plus levamisole were tested for any potential additive or even synergistic interactions. Emodepside had a significantly lower EC50 value than PF1022A in the T. spiralis (0.02788 vs. 0.05862 μg/ml) and the N. brasiliensis (0.06188 vs. 0.1485 μg/ml) motility assays but not in the acetylcholine esterase secretion assay with adult N. brasiliensis (0.05650 vs. 0.06886 μg/ml). While amidantel showed only minimal or at best partial inhibition of nematode motility and acetylcholine esterase secretion, tribendimidine was nearly as potent as deacylated amidantel. Whereas deacylated amidantel had a significantly lower EC50 than tribendimidine in the N. brasiliensis L3 motility assay (0.05492 vs. 0.2080 μg/ml), differences were not significant in the T. spiralis L1 motility assay (0.7766 vs. 1.145 μg/ml). Surprisingly, none of the combinations showed improved efficacy when compared to the individual drugs including levamisole/tribendimidine, which have previously been reported to act synergistically against Ancylostoma ceylanicum.

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Acknowledgements

The Bayer HealthCare AG (Leverkusen, Germany) funded the presented study. The Bayer HealthCare AG sells anthelmintics for the use in veterinary medicine.

Conflict of interest

A. Harder and D. Kulke were employees of Bayer HealthCare AG when the study was conducted. Bayer HealthCare had no influence on the design of the study.

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Authors and Affiliations

  1. Institute for Parasitology and Tropical Veterinary Medicine, Freie Universität Berlin, Königsweg 67, 14163, Berlin, Germany

    Daniel Kulke, Jürgen Krücken, Janina Demeler & Georg von Samson-Himmelstjerna

  2. Department for Biology, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225, Düsseldorf, Germany

    Achim Harder

  3. Institute for Zoomorphology, Cytology and Parasitology, Heinrich-Heine-University Düsseldorf, Universitätsstrasse 1, 40225, Düsseldorf, Germany

    Heinz Mehlhorn

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  1. Daniel Kulke
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Correspondence to Daniel Kulke.

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Kulke, D., Krücken, J., Demeler, J. et al. In vitro efficacy of cyclooctadepsipepdtides and aminophenylamidines alone and in combination against third-stage larvae and adult worms of Nippostrongylus brasiliensis and first-stage larvae of Trichinella spiralis . Parasitol Res 112, 335–345 (2013). https://doi.org/10.1007/s00436-012-3141-1

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  • DOI: https://doi.org/10.1007/s00436-012-3141-1

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