title: RCB20, an experimental benzimidazole derivative, affects tubulin expression and induces gross anatomical changes in Taenia crassiceps cysticerci.
abstract: Helminth β-tubulins are the targets of benzimidazole (BZM) carbamate compounds. The specificity of the interactions between such compounds and their in vivo targets depends on the presence of specific amino acid residues in the target molecules. To discover new and effective anthelmintic drugs, we used a medicinal chemistry approach to synthesize a series of BZM derivatives that exploited the BZM moiety as a template. We have previously found that one compound, 2-(trifluoromethyl)-1H-benzimidazole (RCB20), has better in vitro and in vivo activity than albendazole sulfoxide (ABZSO). In the present study, the effect of RCB20 and ABZSO treatment on expression of Taenia crassiceps cysticerci cytoskeletal proteins such as actin, myosin II, and tubulin isoforms was examined. The effects of RCB20 and ABZSO after 11 days treatment of the parasites was evaluated by light, confocal, and electron microscopy, and by immunochemistry and immunohistochemistry. The RCB20-induced effects were more rapid than the ABZSO-induced effects on the parasites. In the RCB20-treated parasites, we observed gross-structural damage at the whole parasite level, particularly in the inner tissues and flame cells. Changes in the expression patterns of the cytoskeletal proteins, as assessed by immunohistochemistry and immunoblotting, revealed that the most important drug-induced effect on the parasites was a reduction in the expression level of tyrosinated α-tubulins. Our research findings suggest that RCB20 treatment affected posttranslational modification of parasite α-tubulin molecules, which involved removal of the α-tubulin carboxy-terminal tyrosine.
authors.affiliation: Facultad de Medicina, Departamento de Microbiología y Parasitología, Universidad Nacional Autónoma de México, 04510, México, DF, Mexico.
authors.forename: Adrián
authors.initials: A
authors.lastname: Márquez-Navarro
authors.forename: América
authors.initials: A
authors.lastname: Pérez-Reyes
authors.forename: Armando
authors.initials: A
authors.lastname: Zepeda-Rodríguez
authors.forename: Olivia
authors.initials: O
authors.lastname: Reynoso-Ducoing
authors.forename: Alicia
authors.initials: A
authors.lastname: Hernández-Campos
authors.forename: Francisco
authors.initials: F
authors.lastname: Hernández-Luis
authors.forename: Rafael
authors.initials: R
authors.lastname: Castillo
authors.forename: Lilian
authors.initials: L
authors.lastname: Yépez-Mulia
authors.forename: Javier R
authors.initials: JR
authors.lastname: Ambrosio
mesh_terms: D000199:Actins / Q000096:biosynthesis; D015766:Albendazole / Q000031:analogs & derivatives / Q000494:pharmacology; D000818:Animals; D000871:Anthelmintics / Q000494:pharmacology*; D001562:Benzimidazoles / Q000494:pharmacology*; D003552:Cysticercus / Q000033:anatomy & histology / Q000187:drug effects; D015870:Gene Expression / Q000187:drug effects*; D007120:Immunochemistry; D008853:Microscopy; D024462:Myosin Type II / Q000096:biosynthesis; D013621:Taenia / Q000033:anatomy & histology / Q000187:drug effects*; D014404:Tubulin / Q000096:biosynthesis*
chemical_list: C557917:6-chloro-5-(1-naphthyloxy)-2-(trifluoromethyl)-1H-benzimidazole; D000199:Actins; D000871:Anthelmintics; D001562:Benzimidazoles; D014404:Tubulin; D024462:Myosin Type II; D015766:Albendazole; C027186:albendazole sulfoxide