title: In vitro and in vivo activities of dicationic diguanidino compounds against Echinococcus multilocularis metacestodes.
abstract: Alveolar echinococcosis (AE) is a disease predominantly affecting the liver, with metacestodes (larvae) of the tapeworm Echinococcus multilocularis proliferating and exhibiting tumor-like infiltrative growth. For many years, chemotherapeutical treatment against alveolar echinococcosis has relied on the benzimidazoles albendazole and mebendazole, which require long treatment durations and exhibit parasitostatic rather than parasiticidal efficacy. Although benzimidazoles have been and still are beneficial for the patients, there is clearly a demand for alternative and more efficient treatment options. Aromatic dications, more precisely a small panel of di-N-aryl-diguanidino compounds, were screened for efficacy against E. multilocularis metacestodes in vitro. Only those with a thiophene core group were active against metacestodes, while furans were not. The most active compound, DB1127, was further investigated in terms of in vivo efficacy in mice experimentally infected with E. multilocularis metacestodes. This diguanidino compound was effective against AE when administered intraperitoneally but not when applied orally. Thus, thiophene-diguanidino derivatives with improved bioavailability when administered orally could lead to treatment options against AE.
authors.affiliation: Institute of Parasitology, Vetsuisse Faculty, University of Berne, Berne, Switzerland.
authors.forename: Tatiana
authors.initials: T
authors.lastname: Küster
authors.forename: Nadja
authors.initials: N
authors.lastname: Kriegel
authors.forename: David W
authors.initials: DW
authors.lastname: Boykin
authors.forename: Chad E
authors.initials: CE
authors.lastname: Stephens
authors.forename: Andrew
authors.initials: A
authors.lastname: Hemphill
mesh_terms: D000818:Animals; D000923:Anticestodal Agents / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D002478:Cells, Cultured; D002522:Chlorocebus aethiops; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D004445:Echinococcosis, Pulmonary / Q000188:drug therapy; D048210:Echinococcus multilocularis / Q000187:drug effects*; D005260:Female; D005347:Fibroblasts / Q000187:drug effects; D005663:Furans / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology; D019791:Guanidine / Q000008:administration & dosage / Q000031:analogs & derivatives / Q000737:chemistry / Q000494:pharmacology; D006146:Guanidines / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D051379:Mice; D008807:Mice, Inbred BALB C; D021261:Parasitic Sensitivity Tests; D051381:Rats; D013876:Thiophenes / Q000008:administration & dosage / Q000737:chemistry / Q000494:pharmacology*; D014709:Vero Cells
chemical_list: D000923:Anticestodal Agents; C570443:DB1127; D005663:Furans; D006146:Guanidines; D013876:Thiophenes; C520808:diguanidine; D019791:Guanidine