Chiara Borsari, Nuno Santarem, Juan Torrado, Ana Isabel Olías, María Jesús Corral, Catarina Baptista, Sheraz Gul, Markus Wolf, Maria Kuzikov, Bernhard Ellinger, Gesa Witt, Philip Gribbon, Jeanette Reinshagen, Pasquale Linciano, Annalisa Tait, Luca Costantino, Lucio H Freitas-Junior, Carolina B Moraes, Pascoalino Bruno Dos Santos, Laura Maria Alcântara, Caio Haddad Franco, Claudia Danielli Bertolacini, Vanessa Fontana, Paloma Tejera Nevado, Joachim Clos, José María Alunda, Anabela Cordeiro-da-Silva, Stefania Ferrari, Maria Paola Costi
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...
January 27, 2017: European Journal of Medicinal Chemistry