Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae)

Autor(es)

Aleixo de Carvalho, Lara Soares ^[1] ; Geraldo, Reinaldo Barros ^[1] ; de Moraes, Josue ^[2] ; Pinto, Pedro Luiz Silva ^[3] ; Pinto, Priscila de Faria ^[4] ; Pereira, Jr., Olavo dos Santos ^[1] ; Da Silva Filho, Ademar A. ^[1]

Afiliação do(s) autor(es)

^[1] Univ Fed Juiz de Fora, Fac Farm, Dept Ciencias Farmaceut, BR-36015400 Juiz De Fora, MG - Brazil

^[2] Univ Guarulhos, Nucleo Pesquisa Doencas Negligenciadas, BR-07025000 Guarulhos, SP - Brazil

^[3] Adolfo Lutz Inst, Nucleo Enteroparasitas, BR-01246902 Sao Paulo, SP - Brazil

^[4] Univ Fed Juiz de Fora, ICB, Dept Bioquim, BR-36015400 Juiz De Fora, MG - Brazil

• Tipo de documento: Artigo Científico
• Fonte: Experimental Parasitology; v. 159, p. 207-214, DEC 2015.
• Citações Web of Science: 5

Resumo

Schistosomiasis is one of the world's major public health problems, and its treatment is widely dependent on praziquantel (PZQ), the only available drug. Schistosoma mansoni ATP diphosphohydrolases are ecto-enzymes localized on the external tegumental surface of S. mansoni and considered an important target for action of new drugs. In this work, the in vitro schistosomicidal activity of the crude extract of Glycyrrhiza inflata roots (GI) and its isolated compounds echinatin, licoflavone A and licoflavone B were evaluated against S. mansoni adult worms. Results showed that GI (200 mu g/mL) was active against adult schistosomes, causing 100% mortality after 24 h of incubation. Chromatographic fractionation of GI led to isolation of echinatin, licoflavone A and licoflavone B. Licoflavone B (25-100 mu M) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms, without affecting mammalian Vero cells. Confocal laser scanning microscopy showed tegumental morphological alterations and changes on the numbers of tubercles of S. mansoni worms in a dose-dependent manner after incubation with licoflavone B. Licoflavone B also showed high S. mansoni ATPase (IC50 of 23.78 mu M) and ADPase (IC50 of 31.50 mu M) inhibitory activities. Docking studies predicted different interactions between licoflavone B and S. mansoni ATPDase 1, corroborating with the in vitro inhibitory activity. This report demonstrated the first evidence for the schistosomicidal activity of licoflavone B and suggests that its mechanism of action involve the inhibition of S. mansoni ATP diphosphohydrolases. (C) 2015 Elsevier Inc. All rights reserved. (AU)

• Processo FAPESP: 00/11624-5 - Embriologia de Gastropoda: análise em microscopia de varredura laser confocal
• Beneficiário: Toshie Kawano
• Modalidade de apoio: Auxílio à Pesquisa - Programa Equipamentos Multiusuários