Cardamonin, a schistosomicidal chalcone from Piper aduncum L. (Piperaceae) that inhibits Schistosoma mansoni ATP diphosphohydrolase

Cardamonin, a schistosomicidal chalcone from Piper aduncum L. (Piperaceae) that inhibits Schistosoma mansoni ATP diphosphohydrolase

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 adu...

Full description

Saved in:
Bibliographic Details
Published in:Phytomedicine (Stuttgart) Vol. 22; no. 10; pp. 921 - 928
Main Authors: de Castro, Clarissa C.B., Costa, Poliana S., Laktin, Gisele T., de Carvalho, Paulo H.D., Geraldo, Reinaldo B., de Moraes, Josué, Pinto, Pedro L.S., Couri, Mara R.C., Pinto, Priscila de F., Da Silva Filho, Ademar A.
Format: Journal Article
Language:English
Published: Germany Elsevier GmbH 15-09-2015
Urban & Fischer Verlag
Subjects:
Animals
Apyrase
Apyrase - antagonists & inhibitors
Cardamom
Cercopithecus aethiops
Chalcone
Chalcones - pharmacology
Enzyme Inhibitors - pharmacology
Female
Male
Molecular Docking Simulation
Molecular Structure
Piper - chemistry
Piper aduncum
Schistosoma mansoni - drug effects
Schistosoma mansoni - enzymology
Schistosomiasis
Schistosomicidal activity
Schistosomicides - pharmacology
SmATPDases
Vero Cells
Brazil
Schistosomicidal activity
PZQ
PaI-H
Cardamom
Piper aduncum
PaI-A
Apyrase
PaI
PaI-C
SmATPDases
Chalcone
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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 Schistosoma mansoni, the major etiological agent of human schistosomiasis. Purpose: We investigated the in vitro schistosomicidal activity of cardamonin, 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 ATPDase1, in order to investigate its mode of inhibition. Methods: In vitro schistosomicidal assays and confocal laser scanning microscopy were used to evaluate the effects of cardamonin on adult schistosomes. Cell viability was measured by MTT assay, and the S. mansoni ATPase activity was determined spectrophotometrically. Identification of the cardamonin binding site and its interactions on S. mansoni ATPDase1 were made by molecular docking experiments. Results: A bioguided fractionation of the crude extract of P. aduncum was carried out, leading to identification of cardamonin as the active compound, along with pinocembrin and uvangoletin. Cardamonin (25, 50, and 100 µM) 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 µM). 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. [Display omitted]
ISSN:0944-7113
1618-095X
DOI:10.1016/j.phymed.2015.06.009