2. Academic Validation
  3. Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds

Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds

  • Eur J Med Chem. 2017 Jan 27:126:1129-1135. doi: 10.1016/j.ejmech.2016.12.017.
Chiara Borsari 1,  Nuno Santarem 2,  Juan Torrado 3,  Ana Isabel Olías 4,  María Jesús Corral 4,  Catarina Baptista 2,  Sheraz Gul 5,  Markus Wolf 5,  Maria Kuzikov 5,  Bernhard Ellinger 5,  Gesa Witt 6,  Philip Gribbon 7,  Jeanette Reinshagen 5,  Pasquale Linciano 1,  Annalisa Tait 1,  Luca Costantino 1,  Lucio H Freitas-Junior 8,  Carolina B Moraes 8,  Pascoalino Bruno Dos Santos 8,  Laura Maria Alcântara 8,  Caio Haddad Franco 8,  Claudia Danielli Bertolacini 8,  Vanessa Fontana 8,  Paloma Tejera Nevado 9,  Joachim Clos 9,  José María Alunda 4,  Anabela Cordeiro-da-Silva 2,  Stefania Ferrari 1,  Maria Paola Costi 10
Affiliations

Affiliations

  • 1 University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
  • 2 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.
  • 3 Complutense University of Madrid, 28040, Madrid, Spain.
  • 4 Complutense University of Madrid, 28040, Madrid, Spain; Instituto de Investigación Hospital 12 de Octubre, Madrid, Spain.
  • 5 Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany.
  • 6 Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany. Electronic address: Gesa.Witt@ime.fraunhofer.de.
  • 7 Fraunhofer Institute for Molecular Biology and Applied Ecology Screening Port, Hamburg, Germany. Electronic address: Philip.Gribbon@ime.fraunhofer.de.
  • 8 Brazilian Centre for Research in Energy and Materials, Campinas, Brazil.
  • 9 Bernhard Nocht Institute for Tropical Medicine, D-20359, Hamburg, Germany.
  • 10 University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy. Electronic address: mariapaola.costi@unimore.it.
PMID: 28064141 DOI: 10.1016/j.ejmech.2016.12.017
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.

Keywords

Chalcones; Cyclodextrins formulation; Early toxicity studies; Leishmania infantum; Trypanosoma brucei; Trypanosoma cruzi.

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