UMYMFOR   05516
UNIDAD DE MICROANALISIS Y METODOS FISICOS EN QUIMICA ORGANICA
Unidad Ejecutora - UE
artículos
Título:
Structure-activity relationship of hybrids of Cinchona alkaloids and bile acids with in vitro antiplasmodial and antitrypanosomal activities
Autor/es:
LEVERRIER, A.; BERO, J.; CABRERA, J.; FRÉDÉRICH, M.; QUETIN-LECLERCQ, J.; PALERMO, J.
Revista:
EUROPEAN JOURNAL OF MEDICAL CHEMISTRY
Editorial:
ELSEVIER FRANCE-EDITIONS SCIENTIFIQUES MEDICALES ELSEVIER
Referencias:
Lugar: Paris; Año: 2015 vol. 100 p. 10 - 17
ISSN:
0223-5234
Resumen:
In this work, a series of hybrid compounds were tested as antiparasitic substances. These hybrids wereprepared from bile acids and a series of antiparasitic Cinchona alkaloids by the formation of a covalent CeC bond via a decarboxylative BartoneZard reaction between the two entities. The bile acids showedonly weak antiparasitic properties, but all the hybrids exhibited high in vitro activities (IC50: 0.48e5.39 mM) against Trypanosoma brucei. These hybrids were more active than their respective parentalkaloids (up to a 135 fold increase in activity), and displayed good selectivity indices. Aditionally, allthese compounds inhibited the in vitro growth of a chloroquine-sensitive strain of Plasmodium falciparum(3D7: IC50: 36.1 nM to 8.72 mM), and the most active hybrids had IC50s comparable to that of artemisinin(IC50: 36 nM). Some structure-activity relationships among the group of 48 hybrids are discussed. Theincrease in antiparasitic activity may be explained by an improvement in bioavailability, since the morelipophilic derivatives showed the lowest IC50s.