New evidence for tamoxifen as an antischistosomal agent: in vitro, in vivo and target fishing studies

Autor(es)

Silva, Tais C. ^[1] ; Mengarda, Ana C. ^[1] ; Silva, Bianca C. ^[1] ; Relvas-Lima, Thais S. ^[1] ; Rodrigues, Vinicius C. ^[1] ; Salvadori, Maria C. ^[2] ; Teixeira, Fernanda S. ^[2] ; Lopes, Andrey F. S. ^[3] ; Rando, Daniela G. G. ^[3] ; Moraes, Josue de ^[1]

Afiliação do(s) autor(es)

^[1] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, BR-07023070 Guarulhos, SP - Brazil

^[2] Univ Sao Paulo, Inst Fis, Sao Paulo, SP - Brazil

^[3] Univ Fed Sao Paulo, Inst Ciencias Ambientais Quim & Farmaceut, Dept Ciencias Farmaceut, Diadema, SP - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Future Medicinal Chemistry; v. 13, n. 11 JUN 2021.
• Citações Web of Science: 1

Resumo

Background: Praziquantel is the only drug available to treat schistosomiasis, and there is an urgent demand for new anthelmintic agents. Methodology \& results: We conducted in-depth in vitro and in vivo studies and report a target fishing investigation. In vitro, tamoxifen was active against adult and immature worms at low concentrations (<5 mu M). Tamoxifen at a single dose (400 mg/kg) or once daily for five consecutive days (100 mg/kg/day) in mice harboring either adult (patent infection) or juvenile (prepatent infection) significantly reduced worm burden (30-70%) and egg production (70-90%). Target fishing studies revealed propionyl-CoA carboxylase as a potential target for tamoxifen in Schistosoma mansoni and glucose uptake by S. mansoni was also significantly reduced. Conclusion: Our results provide news evidence of antiparasitic effect of tamoxifen and reveal propionyl-CoA carboxylase as a potential target. (AU)

• Processo FAPESP: 16/22488-3 - Reposicionamento de fármacos para doenças negligenciadas: identificação de novos agentes anti-helmínticos
• Beneficiário: Josué de Moraes
• Modalidade de apoio: Auxílio à Pesquisa - Regular
• Processo FAPESP: 19/25905-2 - Avaliação pré-clínica para administração oral de formulações nanoestruturadas contendo fármacos com atividade anti-helmíntica
• Beneficiário: Ana Carolina Araujo Mengarda
• Modalidade de apoio: Bolsas no Brasil - Doutorado
• Processo FAPESP: 19/25289-0 - Atividade anti-helmíntica in vitro do praziquantel e ácido mefenâmico nanocarreados
• Beneficiário: Vinícius de Castro Rodrigues
• Modalidade de apoio: Bolsas no Brasil - Iniciação Científica