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Eur J Med Chem. 2017 Jan 27;126:1129-1135. doi: 10.1016/j.ejmech.2016.12.017. Epub 2016 Dec 9.

Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds.

Author information

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.

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

PMID:
28064141
DOI:
10.1016/j.ejmech.2016.12.017
[Indexed for MEDLINE]

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