title: Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds.
abstract: Chalcones display a broad spectrum of pharmacological activities. Herein, a series of 2'-hydroxy methoxylated chalcones was synthesized and evaluated towards Trypanosoma brucei, Trypanosoma cruzi and Leishmania infantum. Among the synthesized library, compounds 1, 3, 4, 7 and 8 were the most potent and selective anti-T. brucei compounds (EC50= 1.3-4.2 μM, selectivity index >10-fold). Compound 4 showed the best early-tox and antiparasitic profile. The pharmacokinetic studies of compound 4 in BALB/c mice using hydroxypropil-β-cyclodextrins formulation showed a 7.5 times increase in oral bioavailability.
authors.affiliation: University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Borsari
authors.affiliation: Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal and Instituto de Investigação e Inovação em Saúde, Universidade do Porto and Institute for Molecular and Cell Biology, 4150-180, Porto, Portugal.
authors.forename: Nuno
authors.initials: N
authors.lastname: Santarem
authors.affiliation: Complutense University of Madrid, 28040, Madrid, Spain.
authors.forename: Juan
authors.initials: J
authors.lastname: Torrado
authors.affiliation: Complutense University of Madrid, 28040, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: Ana Isabel
authors.initials: AI
authors.lastname: Olías
authors.affiliation: Complutense University of Madrid, 28040, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: María Jesús
authors.initials: MJ
authors.lastname: Corral
authors.affiliation: Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal and Instituto de Investigação e Inovação em Saúde, Universidade do Porto and Institute for Molecular and Cell Biology, 4150-180, Porto, Portugal.
authors.forename: Catarina
authors.initials: C
authors.lastname: Baptista
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany.
authors.forename: Sheraz
authors.initials: S
authors.lastname: Gul
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany.
authors.forename: Markus
authors.initials: M
authors.lastname: Wolf
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany.
authors.forename: Maria
authors.initials: M
authors.lastname: Kuzikov
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany.
authors.forename: Bernhard
authors.initials: B
authors.lastname: Ellinger
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany. Electronic address: Gesa.Witt@ime.fraunhofer.de.
authors.forename: Gesa
authors.initials: G
authors.lastname: Witt
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany. Electronic address: Philip.Gribbon@ime.fraunhofer.de.
authors.forename: Philip
authors.initials: P
authors.lastname: Gribbon
authors.affiliation: Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany.
authors.forename: Jeanette
authors.initials: J
authors.lastname: Reinshagen
authors.affiliation: University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
authors.forename: Pasquale
authors.initials: P
authors.lastname: Linciano
authors.affiliation: University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
authors.forename: Annalisa
authors.initials: A
authors.lastname: Tait
authors.affiliation: University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
authors.forename: Luca
authors.initials: L
authors.lastname: Costantino
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Lucio H
authors.initials: LH
authors.lastname: Freitas-Junior
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Carolina B
authors.initials: CB
authors.lastname: Moraes
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Pascoalino
authors.initials: P
authors.lastname: Bruno Dos Santos
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Laura Maria
authors.initials: LM
authors.lastname: Alcântara
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Caio Haddad
authors.initials: CH
authors.lastname: Franco
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Claudia Danielli
authors.initials: CD
authors.lastname: Bertolacini
authors.affiliation: Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Fontana
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
authors.forename: Paloma
authors.initials: P
authors.lastname: Tejera Nevado
authors.affiliation: Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
authors.forename: Joachim
authors.initials: J
authors.lastname: Clos
authors.affiliation: Complutense University of Madrid, 28040, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
authors.forename: José María
authors.initials: JM
authors.lastname: Alunda
authors.affiliation: Institute for Molecular and Cell Biology, 4150-180 Porto, Portugal and Instituto de Investigação e Inovação em Saúde, Universidade do Porto and Institute for Molecular and Cell Biology, 4150-180, Porto, Portugal.
authors.forename: Anabela
authors.initials: A
authors.lastname: Cordeiro-da-Silva
authors.affiliation: University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
authors.forename: Stefania
authors.initials: S
authors.lastname: Ferrari
authors.affiliation: University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy. Electronic address: mariapaola.costi@unimore.it.
authors.forename: Maria Paola
authors.initials: MP
authors.lastname: Costi
mesh_terms: D000818:Animals; D000977:Antiparasitic Agents / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D045744:Cell Line, Tumor; D047188:Chalcones / Q000737:chemistry* / Q000493:pharmacokinetics / Q000494:pharmacology* / Q000633:toxicity; D003505:Cyclodextrins / Q000737:chemistry; D004337:Drug Carriers / Q000737:chemistry; D051379:Mice; D012995:Solubility; D014351:Trypanosomatina / Q000187:drug effects
chemical_list: D000977:Antiparasitic Agents; D047188:Chalcones; D003505:Cyclodextrins; D004337:Drug Carriers; C013031:2'-hydroxychalcone
keywords: Chalcones; Cyclodextrins formulation; Early toxicity studies; Leishmania infantum; Trypanosoma brucei; Trypanosoma cruzi