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In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes.
Antimicrob Agents Chemother. 2011 Oct; 55(10):4866-72.AA

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.

Authors+Show Affiliations

Institute of Parasitology, Vetsuisse Faculty, University of Berne, Langgass-Strasse 122, CH-3012 Berne, Switzerland.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

21768518

Citation

Stadelmann, Britta, et al. "In Vitro Efficacy of Dicationic Compounds and Mefloquine Enantiomers Against Echinococcus Multilocularis Metacestodes." Antimicrobial Agents and Chemotherapy, vol. 55, no. 10, 2011, pp. 4866-72.
Stadelmann B, Küster T, Scholl S, et al. In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes. Antimicrob Agents Chemother. 2011;55(10):4866-72.
Stadelmann, B., Küster, 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), 4866-72. https://doi.org/10.1128/AAC.00478-11
Stadelmann B, et al. In Vitro Efficacy of Dicationic Compounds and Mefloquine Enantiomers Against Echinococcus Multilocularis Metacestodes. Antimicrob Agents Chemother. 2011;55(10):4866-72. PubMed PMID: 21768518.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - In vitro efficacy of dicationic compounds and mefloquine enantiomers against Echinococcus multilocularis metacestodes. AU - Stadelmann,Britta, AU - Küster,Tatiana, AU - Scholl,Sabrina, AU - Barna,Fabienne, AU - Kropf,Christian, AU - Keiser,Jennifer, AU - Boykin,David W, AU - Stephens,Chad E, AU - Hemphill,Andrew, Y1 - 2011/07/18/ PY - 2011/7/20/entrez PY - 2011/7/20/pubmed PY - 2012/3/7/medline SP - 4866 EP - 72 JF - Antimicrobial agents and chemotherapy JO - Antimicrob. Agents Chemother. VL - 55 IS - 10 N2 - 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. SN - 1098-6596 UR - https://www.unboundmedicine.com/medline/citation/21768518/In_vitro_efficacy_of_dicationic_compounds_and_mefloquine_enantiomers_against_Echinococcus_multilocularis_metacestodes_ L2 - http://aac.asm.org/cgi/pmidlookup?view=long&pmid=21768518 DB - PRIME DP - Unbound Medicine ER -