甲氧基化2'-羟基查耳酮作为抗寄生虫先导化合物。
Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds.
作者信息
Borsari Chiara, Santarem Nuno, Torrado Juan, Olías Ana Isabel, Corral María Jesús, Baptista Catarina, Gul Sheraz, Wolf Markus, Kuzikov Maria, Ellinger Bernhard, Witt Gesa, Gribbon Philip, Reinshagen Jeanette, Linciano Pasquale, Tait Annalisa, Costantino Luca, Freitas-Junior Lucio H, Moraes Carolina B, Bruno Dos Santos Pascoalino, Alcântara Laura Maria, Franco Caio Haddad, Bertolacini Claudia Danielli, Fontana Vanessa, Tejera Nevado Paloma, Clos Joachim, Alunda José María, Cordeiro-da-Silva Anabela, Ferrari Stefania, Costi Maria Paola
机构信息
University of Modena and Reggio Emilia, Via Campi 103, 41125, Modena, Italy.
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.
出版信息
Eur J Med Chem. 2017 Jan 27;126:1129-1135. doi: 10.1016/j.ejmech.2016.12.017. Epub 2016 Dec 9.
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 (EC = 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.
查耳酮具有广泛的药理活性。在此，合成了一系列2'-羟基甲氧基化查耳酮，并对布氏锥虫、克氏锥虫和婴儿利什曼原虫进行了评估。在合成文库中，化合物1、3、4、7和8是最有效的选择性抗布氏锥虫化合物（EC = 1.3 - 4.2 μM，选择性指数>10倍）。化合物4表现出最佳的早期毒性和抗寄生虫特性。使用羟丙基-β-环糊精制剂对化合物4在BALB/c小鼠中进行的药代动力学研究表明，口服生物利用度提高了7.5倍。
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