Phenotypic screening of nonsteroidal anti-inflammatory drugs identified mefenamic acid as a drug for the treatment of schistosomiasis

Autor(es):Mostrar menos -

Lago, Eloi M. ^[1] ; Silva, Marcos P. ^[1] ; Queiroz, Talita G. ^[1] ; Mazlouma, Susana F. ^[1] ; Rodrigues, Vinicius C. ^[1] ; Carnauba, Paulo U. ^[1] ; Pinto, Pedro L. ^[2] ; Rocha, Jefferson A. ^[3] ; Ferreira, Leonardo L. G. ^[4] ; Andricopulo, Adriano D. ^[4] ; de Moraes, Josue ^[1]

Afiliação do(s) autor(es)

^[1] Univ Guarulhos, Res Ctr Neglected Dis, Praca Tereza Cristina 229, BR-07023070 Guarulhos, SP - Brazil

^[2] Adolfo Lutz Inst, Ctr Res Parasitol, Sao Paulo, SP - Brazil

^[3] Univ Fed Maranhao, Res Grp Nat Sci & Biotechnol, Grajau, MA - Brazil

^[4] Univ Sao Paulo, Lab Med & Computat Chem, Ctr Res & Innovat Biodivers & Drug Discovery, Phys Inst Sao Carlos, Sao Carlos, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: EBIOMEDICINE; v. 43, p. 370-379, MAY 2019.
• Citações Web of Science: 0

Resumo

Background: Treatment and control of schistosomiasis, one of the most insidious and serious parasitic diseases, depend almost entirely on a single drug, praziquantel. Since the funding for drug development for poverty-associated diseases is very limited, drug repurposing is a promising strategy. In this study, 73 nonsteroidal anti-inflammatory drugs (NSAIDs) commonly used in medical and veterinary fields were evaluated for their anti-schistosomal properties. Methods: The efficacy of NSAIDs was first tested against adult Schistosoma mansoni ex vivo using phenotypic screening strategy, effective drugs were further tested in a murine model of schistosomiasis. The disease parameters measured were worm and egg burden, hepato- and splenomegaly. Findings: From 73 NSAIDs, five (mefenamic add, tolfenamic acid, meclofenamic acid, celecoxib, and diclofenac) were identified to effectively kill schistosomes. These results were further supported by scanning electron microscopy analysis. In addition, the octanol-water partition coefficient, both for neutral and ionized species, revealed to be a critical property for the ex vivo activity profile. Compounds were then tested in vivo using both patent and a prepatent S. mansoni infection in a mouse model. The most effective NSAID was mefenamic acid, which highly reduced worm burden, egg production, and hepato- and splenomegaly. interpretation: The treatment regimen used in this study is within the range for which mefenamic acid has been used in dinical practice, thus, it is demonstrated the capacity of mefenamic acid to act as a potent anti-schistosomal agent suitable for dinical repurposing in the treatment of schistosomiasis. (C) 2019 The Authors. Published by Elsevier B.V. (AU)

• Processo FAPESP: 13/07600-3 - CIBFar - Centro de Inovação em Biodiversidade e Fármacos
• Beneficiário: Glaucius Oliva
• Linha de fomento: Auxílio à Pesquisa - Centros de Pesquisa, Inovação e Difusão - CEPIDs
• Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
• Beneficiário: Josué de Moraes
• Linha de fomento: Auxílio à Pesquisa - Regular