Analysis of the effect of a 2-(trifluoromethyl)-1H-benzimidazole derivative on Trichinella spiralis muscle larvae.

Abstract

Albendazole and mebendazole are widely used in the treatment of trichinellosis; however, chemotherapy failure has been reported. In an effort to develop new anthelminthic compounds, we examined a previously synthesized 2-(trifluoromethyl)-1H-benzimidazole derivative (1) that showed good in vitro activity against Trichinella spiralis muscle larvae but low in vivo efficacy. In order to improve the solubility of compound 1, an inclusion complex with 2-hydroxypropyl-β-cyclodextrin (1/HP-βCD) was prepared. When 1/HP-βCD was tested in vivo, it significantly reduced the ML burden (84%). In addition, a proteomic analysis of T. spiralis ML treated with 1 revealed significant changes in the expression levels of proteins involved in energy metabolism and the cytoskeleton of the parasite. Compound (1) also induced extensive ultrastructural changes in the cuticle, hypodermis and midgut of the parasite.

• Authors: Félix Matadamas-Martínez, Benjamín Nogueda-Torres, Alicia Hernández-Campos, Francisco Hernández-Luis, Rafael Castillo, Guillermo Mendoza, Javier R Ambrosio, Gabriela Andrés-Antonio, Lilián Yépez-Mulia
• Journal: Veterinary parasitology (Vet Parasitol) Vol. 194 Issue 2-4 Pg. 193-7 (May 20 2013) ISSN: 1873-2550 [Electronic] Netherlands
• PMID: 23462252 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2013 Elsevier B.V. All rights reserved.

Chemical References

• Anthelmintics
• Benzimidazoles
• beta-Cyclodextrins
• 2-Hydroxypropyl-beta-cyclodextrin

Topics

• 2-Hydroxypropyl-beta-cyclodextrin
• Animals
• Anthelmintics (pharmacology)
• Benzimidazoles (pharmacology)
• Electrophoresis, Gel, Two-Dimensional
• Gene Expression Regulation (drug effects)
• Larva
• Mass Spectrometry
• Mice
• Mice, Inbred BALB C
• Microscopy, Electron, Transmission
• Muscles (parasitology)
• Proteomics
• Trichinella spiralis (drug effects, ultrastructure)
• Trichinellosis (drug therapy, parasitology)
• beta-Cyclodextrins (pharmacology)