In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes

Britta Stadelmann, Tatiana Küster, Sabrina Scholl, Fabienne Barna, Christian Kropf, Jennifer Keiser, David W. Boykin, Chad E. Stephens, Andrew Hemphill

Research output: Contribution to journalArticle

27 Citations (Scopus)

Abstract

The current chemotherapy of alveolar echinococcosis (AE) is based on benzimidazoles such as albendazole and has been shown to be parasitostatic rather than parasiticidal, requiring lifelong duration. Thus, new and more efficient treatment options are urgently needed. By employing a recently validated assay based on the release of functional phosphoglucose isomerase (PGI) from dying parasites, the activities of 26 dicationic compounds and of the (+)- and (-)-erythro-enantiomers of mefloquine were investigated. Initial screening of compounds was performed at 40 μM, and those compounds exhibiting considerable antiparasitic activities were also assessed at lower concentrations. Of the dicationic drugs, DB1127 (a diguanidino compound) with activities comparable to nitazoxanide was further studied. The activity of DB1127 was dose dependent and led to severe structural alterations, as visualized by electron microscopy. The (+)- and (-)-erythro-enantiomers of mefloquine showed similar dose-dependent effects, although higher concentrations of these compounds than of DB1127 were required for metacestode damage. In conclusion, of the drugs investigated here, the diguanidino compound DB1127 represents the most promising compound for further study in appropriate in vivo models for Echinococcus multilocularis infection.

Original languageEnglish (US)
Pages (from-to)4866-4872
Number of pages7
JournalAntimicrobial Agents and Chemotherapy
Volume55
Issue number10
DOIs
StatePublished - Oct 1 2011

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Echinococcus multilocularis
Mefloquine
nitazoxanide
Benzimidazoles
Glucose-6-Phosphate Isomerase
Antiparasitic Agents
Albendazole
Pharmaceutical Preparations
Electron Microscopy
Parasites
Drug Therapy
DB1127
In Vitro Techniques
Infection

ASJC Scopus subject areas

  • Pharmacology
  • Pharmacology (medical)
  • Infectious Diseases

Cite this

In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes. / Stadelmann, Britta; Küster, Tatiana; Scholl, Sabrina; Barna, Fabienne; Kropf, Christian; Keiser, Jennifer; Boykin, David W.; Stephens, Chad E.; Hemphill, Andrew.

In: Antimicrobial Agents and Chemotherapy, Vol. 55, No. 10, 01.10.2011, p. 4866-4872.

Research output: Contribution to journalArticle

Stadelmann, B, Küster, T, Scholl, S, Barna, F, Kropf, C, Keiser, J, Boykin, DW, Stephens, CE & Hemphill, A 2011, 'In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes', Antimicrobial Agents and Chemotherapy, vol. 55, no. 10, pp. 4866-4872. https://doi.org/10.1128/AAC.00478-11
Stadelmann, Britta ; Küster, Tatiana ; Scholl, Sabrina ; Barna, Fabienne ; Kropf, Christian ; Keiser, Jennifer ; Boykin, David W. ; Stephens, Chad E. ; Hemphill, Andrew. / In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes. In: Antimicrobial Agents and Chemotherapy. 2011 ; Vol. 55, No. 10. pp. 4866-4872.
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