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 = 13-4.2 mu M, 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-beta-cyclodextrins formulation showed a 7.5 times increase in oral bioavailability.
Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds / C. Borsari, N. Santarem, J. Torrado, A.I. Olias, M.J. Corral, C. Baptista, S. Gul, M. Wolf, M. Kuzikov, B. Ellinger, G. Witt, P. Gribbon, J. Reinshagen, P. Linciano, A. Tait, L. Costantino, L.H. Freitas-Junior, C.B. Moraes, P. Bruno dos Santos, L.M. Alcantara, C.H. Franco, C.D. Bertolacini, V. Fontana, P. Tejera Nevado, J. Clos, J.M. Alunda, A. Cordeiro-da-Silva, S. Ferrari, M.P. Costi. - In: EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY. - ISSN 0223-5234. - 126:(2017 Jan 27), pp. 1129-1135. [10.1016/j.ejmech.2016.12.017]
Methoxylated 2'-hydroxychalcones as antiparasitic hit compounds
C. BorsariPrimo
;
2017
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 = 13-4.2 mu M, 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-beta-cyclodextrins formulation showed a 7.5 times increase in oral bioavailability.
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