Nepveu Françoise, Kim S., Boyer J., Chatriant O., Ibrahim H., Reybier K., Monje M. C., Chevalley Sèverine, Perio P., Lajoie B. H., Bouajila J., Deharo Eric, Sauvain Michel, Tahar Rachida, Basco Leonardo, Pantaleo A., Turini F., Arese P., Valentin A., Thompson E., Vivas L., Petit S., Nallet J. P. (2010). Synthesis and antiplasmodial activity of new indolone N-oxide derivatives. Journal of Medicinal Chemistry, 53 (2), p. 699-714. ISSN 0022-2623.
Titre du document
Synthesis and antiplasmodial activity of new indolone N-oxide derivatives
Année de publication
2010
Auteurs
Nepveu Françoise, Kim S., Boyer J., Chatriant O., Ibrahim H., Reybier K., Monje M. C., Chevalley Sèverine, Perio P., Lajoie B. H., Bouajila J., Deharo Eric, Sauvain Michel, Tahar Rachida, Basco Leonardo, Pantaleo A., Turini F., Arese P., Valentin A., Thompson E., Vivas L., Petit S., Nallet J. P.
Source
Journal of Medicinal Chemistry, 2010,
53 (2), p. 699-714 ISSN 0022-2623
A series of 66 new indolone-N-oxide derivatives was synthesized with three different methods. Compounds were evaluated for in vitro activity against CQ-sensitive (3D7), CQ-resistant (FcB1), and CQ and pyrimethamine cross-resistant (K1) strains of Plasmodium falciparum (P.f.), its well as for cytotoxic concentration (CC50) on MCF7 and KB human tumor Cell lines. Compound 26 (5-methoxy-indolone-N-oxide analogue) had the most potent antiplasmodial activity in vitro (< 3 nM on FcB1 and = 1.7 nM on 3D7) with a very satisfactory selectivity index (CC50 MCF7/IC50 FcB1: 14623; CC50 KB/IC50 3D7: 198823). In in vivo experiments, compound 1 (dioxymethylene derivatives of the indolone-N-oxide) showed the best antiplasmodial activity against Plasmodium berghei, 62% inhibition of the parasitaemia at 30 mg/kg/day.
Plan de classement
Sciences fondamentales / Techniques d'analyse et de recherche [020]
;
Entomologie médicale / Parasitologie / Virologie [052]
Identifiant IRD
PAR00004660
