Publications des scientifiques de l'IRD

Quiliano M., Pabon A., Moles E., Bonilla-Ramirez L., Fabing I., Fong K. Y., Nieto-Aco D. A., Wright D. W., Pizarro J. C., Vettorazzi A., de Cerain A. L., Deharo Eric, Fernandez-Busquets X., Garavito G., Aldana I., Galiano S. (2018). Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives : synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery. European Journal of Medicinal Chemistry, 152, p. 489-514. ISSN 0223-5234.

Titre du document
Structure-activity relationship of new antimalarial 1-aryl-3-susbtituted propanol derivatives : synthesis, preliminary toxicity profiling, parasite life cycle stage studies, target exploration, and targeted delivery
Année de publication
2018
Type de document
Article référencé dans le Web of Science WOS:000435048900037
Auteurs
Quiliano M., Pabon A., Moles E., Bonilla-Ramirez L., Fabing I., Fong K. Y., Nieto-Aco D. A., Wright D. W., Pizarro J. C., Vettorazzi A., de Cerain A. L., Deharo Eric, Fernandez-Busquets X., Garavito G., Aldana I., Galiano S.
Source
European Journal of Medicinal Chemistry, 2018, 152, p. 489-514 ISSN 0223-5234
Design, synthesis, structure-activity relationship, cytotoxicity studies, in silico drug-likeness, genotoxicity screening, and in vivo studies of new 1-aryl-3-substituted propanol derivatives led to the identification of nine compounds with promising in vitro (55, 56, 61, 64, 66, and 70-73) and in vivo (66 and 72) antimalarial profiles against Plasmodium falciparum and Plasmodium berghei. Compounds 55, 56, 61, 64, 66 and 70-73 exhibited potent antiplasmodial activity against chloroquine-resistant strain FCR-3 (IC(50)s <0.28 mu M), and compounds 55, 56, 64, 70, 71, and 72 showed potent biological activity in chloroquine-sensitive and multidrug-resistant strains (IC(50)s < 0.7 mu M for 3D7, D6, FCR-3 and C235). All of these compounds share appropriate drug-likeness profiles and adequate selectivity indexes (77 < SI < 184) as well as lack genotoxicity. In vivo efficacy tests in a mouse model showed compounds 66 and 72 to be promising candidates as they exhibited significant parasitemia reductions of 96.4% and 80.4%, respectively. Additional studies such as liver stage and sporogony inhibition, target exploration of heat shock protein 90 of P. falciparum, targeted delivery by immunoliposomes, and enantiomer characterization were performed and strongly reinforce the hypothesis of 1-aryl-3-substituted propanol derivatives as promising antimalarial compounds.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020] ; Santé : généralités [050] ; Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010073135]
Identifiant IRD
fdi:010073135
Contact