In Vitro Analysis of Albendazole Sulfoxide Enantiomers Shows that (+)-(R)-Albendazole Sulfoxide Is the Active Enantiomer against Taenia solium

Autor(es):Mostrar menos -

Paredes, Adriana ^[1] ; Lourenco, Tiago de Campos ^[2] ; Marzal, Miguel ^[1] ; Rivera, Andrea ^[1] ; Dorny, Pierre ^[3] ; Mahanty, Siddhartha ^{[1, 4]} ; Guerra-Giraldez, Cristina ^{[1, 5]} ; Garcia, Hector H. ^{[1, 5, 6]} ; Nash, Theodore E. ^{[1, 4]} ; Cass, Quezia B. ^[2] ; Peru, Cysticercosis Working Grp

Afiliação do(s) autor(es)

^[1] Univ Peruana Cayetano Heredia, Lab Inmunopatol Neurocisticercosis, Fac Ciencias & Filosofia, Lima - Peru

^[2] Univ Fed Sao Carlos, Dept Quim, Sao Paulo - Brazil

^[3] Inst Trop Med, Dept Biomed Sci, B-2000 Antwerp - Belgium

^[4] NIAID, Parasit Dis Lab, NIH, Bethesda, MD 20892 - USA

^[5] Univ Peruana Cayetano Heredia, Fac Ciencias & Filosofia, Dept Ciencias Celulares & Mol, Lima - Peru

^[6] Inst Nacl Ciencias Neurol, Unidad Cisticercosis, Lima - Peru

• Tipo de documento: Artigo Científico
• Fonte: Antimicrobial Agents and Chemotherapy; v. 57, n. 2, p. 944-949, FEB 2013.
• Citações Web of Science: 9

Resumo

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. (AU)

• Processo FAPESP: 09/18515-1 - Cromatografia de leito móvel simulado com comprimento de zona variável (Varicol): estudo de caso para a purificação de misturas enantioméricas
• Beneficiário: Tiago de Campos Lourenço
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 07/02872-4 - Aplicação da cromatografia de leito móvel simulado com comprimento de zona variável (Varicol) na obtenção de enantiômeros de compostos biologicamente ativos
• Beneficiário: Cesar Costapinto Santana
• Modalidade de apoio: Auxílio à Pesquisa - Temático