title: In vitro analysis of albendazole sulfoxide enantiomers shows that (+)-(R)-albendazole sulfoxide is the active enantiomer against Taenia solium.
abstract: Albendazole is an anthelmintic drug widely used in the treatment of neurocysticercosis (NCC), an infection of the brain with Taenia solium cysts. However, drug levels of its active metabolite, albendazole sulfoxide (ABZSO), are erratic, likely resulting in decreased efficacy and suboptimal cure rates in NCC. Racemic albendazole sulfoxide is composed of ABZSO (+)-(R)- and (-)-(S) enantiomers that have been shown to differ in pharmacokinetics and activity against other helminths. The antiparasitic activities of racemic ABZSO and its (+)-(R)- and (-)-(S) enantiomers against T. solium cysts were evaluated in vitro. Parasites were collected from naturally infected pigs, cultured, and exposed to the racemic mixture or to each enantiomer (range, 10 to 500 ng/ml) or to praziquantel as a reference drug. The activity of each compound against cysts was assayed by measuring the ability to evaginate and inhibition of alkaline phosphatase (AP) and parasite antigen release. (+)-(R)-ABZSO was significantly more active than (-)-(S)-ABZSO in suppressing the release of AP and antigen into the supernatant in a dose- and time-dependent manner, indicating that most of the activity of ABZSO resides in the (+)-(R) enantiomer. Use of this enantiomer alone may lead to increased efficacy and/or less toxicity compared to albendazole.
authors.affiliation: Laboratorio de Inmunopatología en Neurocisticercosis, Facultad de Ciencias y Filosofía, Universidad Peruana Cayetano Heredia, Lima, Perú
authors.forename: Adriana
authors.initials: A
authors.lastname: Paredes
authors.forename: Tiago
authors.initials: T
authors.lastname: de Campos Lourenço
authors.forename: Miguel
authors.initials: M
authors.lastname: Marzal
authors.forename: Andrea
authors.initials: A
authors.lastname: Rivera
authors.forename: Pierre
authors.initials: P
authors.lastname: Dorny
authors.forename: Siddhartha
authors.initials: S
authors.lastname: Mahanty
authors.forename: Cristina
authors.initials: C
authors.lastname: Guerra-Giraldez
authors.forename: Hector H
authors.initials: HH
authors.lastname: García
authors.forename: Theodore E
authors.initials: TE
authors.lastname: Nash
authors.forename: Quezia B
authors.initials: QB
authors.lastname: Cass
mesh_terms: D015766:Albendazole / Q000031:analogs & derivatives* / Q000737:chemistry / Q000494:pharmacology / Q000627:therapeutic use; D000469:Alkaline Phosphatase / Q000037:antagonists & inhibitors; D000818:Animals; D000923:Anticestodal Agents / Q000737:chemistry* / Q000494:pharmacology* / Q000627:therapeutic use; D020019:Neurocysticercosis / Q000188:drug therapy*; D011223:Praziquantel / Q000494:pharmacology; D013237:Stereoisomerism; D013552:Swine; D041201:Taenia solium / Q000187:drug effects*
chemical_list: D000923:Anticestodal Agents; D011223:Praziquantel; D000469:Alkaline Phosphatase; D015766:Albendazole; C027186:albendazole sulfoxide