title: Schistosomicidal activity and docking of Schistosoma mansoni ATPDase 1 with licoflavone B isolated from Glycyrrhiza inflata (Fabaceae).
abstract: 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 μg/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 μM) 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 μM) and ADPase (IC50 of 31.50 μM) 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.
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: Lara Soares
authors.initials: LS
authors.lastname: Aleixo de Carvalho
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: Reinaldo Barros
authors.initials: RB
authors.lastname: Geraldo
authors.affiliation: Núcleo de Pesquisa em Doenças Negligenciadas, Universidade Guarulhos, 07025-000, Guarulhos, SP, Brazil.
authors.forename: Josué
authors.initials: J
authors.lastname: de Moraes
authors.affiliation: Núcleo de Enteroparasitas, Instituto Adolfo Lutz, 01246-902, São Paulo, SP, Brazil.
authors.forename: Pedro Luiz
authors.initials: PL
authors.lastname: Silva Pinto
authors.affiliation: Departamento de Bioquímica/ICB, Universidade Federal de Juiz de Fora, 36015-400, Juiz de Fora, MG, Brazil.
authors.forename: Priscila
authors.initials: P
authors.lastname: de Faria Pinto
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil.
authors.forename: Olavo dos Santos
authors.initials: Odos S
authors.lastname: Pereira
authors.affiliation: Departamento de Ciências Farmacêuticas, Faculdade de Farmácia, Universidade Federal de Juiz de Fora, Juiz de Fora, MG, Brazil. Electronic address: ademar.alves@ufjf.edu.br.
authors.forename: Ademar A
authors.initials: AA
authors.lastname: Da Silva Filho
mesh_terms: D000818:Animals; D001081:Apyrase / Q000037:antagonists & inhibitors*; D001700:Biomphalaria; D006224:Cricetinae; D005260:Female; D047309:Flavones / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D006035:Glycyrrhiza / Q000737:chemistry*; D008297:Male; D008647:Mesocricetus; D010936:Plant Extracts / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*; D018517:Plant Roots / Q000737:chemistry; D012098:Reproduction; D012550:Schistosoma mansoni / Q000187:drug effects* / Q000201:enzymology; D012556:Schistosomicides / Q000737:chemistry / Q000302:isolation & purification / Q000494:pharmacology*
chemical_list: D047309:Flavones; D010936:Plant Extracts; D012556:Schistosomicides; C000606815:licoflavone B; D001081:Apyrase
keywords: Apyrase; Flavonoids; Licorice; Schistosoma mansoni ATP diphosphohydrolase