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

Author(s)

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]

Affiliation

^[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

• Document type: Journal article
• Source: Future Medicinal Chemistry; v. 13, n. 11 JUN 2021.
• Web of Science Citations: 1

Abstract

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)

• FAPESP's process: 16/22488-3 - Drug repositioning for neglected diseases: identification of novel anthelmintic agents
• Grantee: Josué de Moraes
• Support Opportunities: Regular Research Grants
• FAPESP's process: 19/25905-2 - Preclinical evaluation for oral administration of nanostructured formulations containing drugs with anthelmintic activity
• Grantee: Ana Carolina Araujo Mengarda
• Support Opportunities: Scholarships in Brazil - Doctorate
• FAPESP's process: 19/25289-0 - In vitro anthelmintic activity of praziquantel and mefenamic acid nanocarreated
• Grantee: Vinícius de Castro Rodrigues
• Support Opportunities: Scholarships in Brazil - Scientific Initiation