Publications des scientifiques de l'IRD

Quiliano M., Mendoza A., Fong K. Y., Pabon A., Goldfarb N. E., Fabing I., Vettorazzi A., de Cerain A. L., Dunn B. M., Garavito G., Wright D. W., Deharo Eric, Perez-Silanes S., Aldana I., Galiano S. (2016). Exploring the scope of new arylamino alcohol derivatives : synthesis, antimalarial evaluation, toxicological studies, and target exploration. International Journal for Parasitology-Drugs and Drug Resistance, 6 (3), p. 184-198. ISSN 2211-3207.

Titre du document
Exploring the scope of new arylamino alcohol derivatives : synthesis, antimalarial evaluation, toxicological studies, and target exploration
Année de publication
2016
Type de document
Article référencé dans le Web of Science WOS:000393046300007
Auteurs
Quiliano M., Mendoza A., Fong K. Y., Pabon A., Goldfarb N. E., Fabing I., Vettorazzi A., de Cerain A. L., Dunn B. M., Garavito G., Wright D. W., Deharo Eric, Perez-Silanes S., Aldana I., Galiano S.
Source
International Journal for Parasitology-Drugs and Drug Resistance, 2016, 6 (3), p. 184-198 ISSN 2211-3207
Synthesis of new 1-aryl-3-substituted propanol derivatives followed by structure-activity relationship, in silico drug-likeness, cytotoxicity, genotoxicity, in silico metabolism, in silico pharmacophore modeling, and in vivo studies led to the identification of compounds 22 and 23 with significant in vitro anti-plasmodial activity against drug sensitive (D6 IC50 <= 0.19 mu M) and multidrug resistant (FCR-3 IC50 <= 0.40 mu M and C235 IC50 <= 0.28 mu M) strains of Plasmodium falciparum. Adequate selectivity index and absence of genotoxicity was also observed. Notably, compound 22 displays excellent parasitemia reduction (98 +/- 1%), and complete cure with all treated mice surviving through the entire period with no signs of toxicity. One important factor is the agreement between in vitro potency and in vivo studies. Target exploration was performed; this chemotype series exhibits an alternative antimalarial mechanism.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020] ; Entomologie médicale / Parasitologie / Virologie [052]
Localisation
Fonds IRD [F B010068947]
Identifiant IRD
fdi:010068947
Contact