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

Lundström-Stadelmann, Britta; Kuster, T.; Scholl, S.; Barna, F.; Kropf, C.; Keiser, J.; Boykin, D.W.; Stephens, C.E.; Hemphill, A. (2011). In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes. Antimicrobial agents and chemotherapy, 55(10), pp. 4866-72. Washington, D.C.: American Society for Microbiology 10.1128/AAC.00478-11

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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 muM, 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.

Item Type:

Journal Article (Original Article)

Division/Institute:

05 Veterinary Medicine > Research Foci > Host-Pathogen Interaction
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP) > Institute of Parasitology
05 Veterinary Medicine > Department of Infectious Diseases and Pathobiology (DIP)

UniBE Contributor:

Lundström Stadelmann, Britta; Küster, Tatiana; Barna, Fabienne; Kropf, Christian and Hemphill, Andrew

Subjects:

600 Technology > 630 Agriculture

ISSN:

0066-4804

Publisher:

American Society for Microbiology

Language:

English

Submitter:

Factscience Import

Date Deposited:

04 Oct 2013 14:31

Last Modified:

15 Jan 2019 09:17

Publisher DOI:

10.1128/AAC.00478-11

Web of Science ID:

000294952600050

URI:

https://boris.unibe.ch/id/eprint/12116 (FactScience: 218399)

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