| Texto completo | |
| Autor(es): |
de Castro, Clarissa C. B.
[1]
;
Costa, Poliana S.
[1]
;
Laktin, Gisele T.
[1]
;
de Carvalho, Paulo H. D.
[1]
;
Geraldo, Reinaldo B.
[1]
;
de Moraes, Josue
[2]
;
Pinto, Pedro L. S.
[3]
;
Couri, Mara R. C.
[4]
;
Pinto, Priscila de F.
[5]
;
Da Silva Filho, Ademar A.
[1]
Número total de Autores: 10
|
| Afiliação do(s) autor(es): | [1] Univ Fed Juiz de Fora, Fac Farm, Dept Ciencias Farmaceut, BR-36036900 Juiz De Fora, MG - Brazil
[2] Nucleo Pesquisa Doencas Negligenciadas FACIG, BR-07025000 Guarulhos, SP - Brazil
[3] Adolfo Lutz Inst, Nucleo Enteroparasitas, BR-01246902 Sao Paulo, SP - Brazil
[4] Univ Fed Juiz de Fora, Dept Quim, BR-36036330 Juiz De Fora, MG - Brazil
[5] Univ Fed Juiz de Fora, Inst Ciencias Biol, Dept Bioquim, BR-36036900 Juiz De Fora, MG - Brazil
Número total de Afiliações: 5
|
| Tipo de documento: | Artigo Científico |
| Fonte: | Phytomedicine; v. 22, n. 10, p. 921-928, SEP 15 2015. |
| Citações Web of Science: | 16 |
| Resumo | |
Background: Schistosomiasis is one of the world's major public health problems, and praziquantel (PZQ) is the only available drug to treat this neglected disease with an urgent demand for new drugs. Recent studies indicated that extracts from Piper aduncum L. (Piperaceae) are active against adult worms of Schistosorna mansoni, the major etiological agent of human schistosomiasis. Purpose: We investigated the in vitro schistosomicidal activity of cardarnonin, a chalcone isolated from the crude extract of P. aduncum. Also, this present work describes, for the first time, the S. mansoni ATP diphosphohydrolase inhibitory activity of cardamonin, as well as, its molecular docking with S. mansoni ATPDase 1, in order to investigate its mode of inhibition. Methods: In vitro schistosomicicial assays and confocal laser scanning microscopy were used to evaluate the effects of cardamonin on adult schistosomes. Cell viability was measured by MIT assay, and the S. mansoni ATPase activity was determined spectrophotometrically. Identification of the cardamonin binding site and its interactions on S. mansoni ATPDasel were made by molecular docking experiments. Results: A bioguided fractionation of the crude extract of P. aduncum was carried out, leading to identification of carciamonin as the active compound, along with pinocembrin and uvangoletin. Carciamonin (25, 50, and 100 mu M) caused 100% mortality, tegumental alterations, and reduction of oviposition and motor activity of all adult worms of S. mansoni, without affecting mammalian 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. Cardamonin also inhibited S. mansoni ATP diphosphohydrolase (IC50 of 23.54 It M). Molecular docking studies revealed that cardamonin interacts with the Nucleotide-Binding of SmATPDase 1. The nature of SmATPDase 1-cardamonin interactions is mainly hydrophobic and hydrogen bonding. Conclusion: This report provides evidence for the in vitro schistosomicidal activity of cardamonin and demonstrated, for the first time, that this chalcone is highly effective in inhibiting S. mansoni ATP diphosphohydrolase, opening the route to further studies of chalcones as prototypes for new S. mansoni ATP diphosphohydrolase inhibitors. (C) 2015 Elsevier GmbH. 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 |