%0 Journal Article
%9 ACL : Articles dans des revues avec comité de lecture répertoriées par l'AERES
%A Nepveu, Françoise
%A Kim, S.
%A Boyer, J.
%A Chatriant, O.
%A Ibrahim, H.
%A Reybier, K.
%A Monje, M. C.
%A Chevalley, Sèverine
%A Perio, P.
%A Lajoie, B. H.
%A Bouajila, J.
%A Deharo, Eric
%A Sauvain, Michel
%A Tahar, Rachida
%A Basco, Leonardo
%A Pantaleo, A.
%A Turini, F.
%A Arese, P.
%A Valentin, A.
%A Thompson, E.
%A Vivas, L.
%A Petit, S.
%A Nallet, J. P.
%T Synthesis and antiplasmodial activity of new indolone N-oxide derivatives
%D 2010
%L PAR00004660
%G ENG
%J Journal of Medicinal Chemistry
%@ 0022-2623
%M ISI:000273672100017
%N 2
%P 699-714
%R 10.1021/jm901300d
%U https://www.documentation.ird.fr/hor/PAR00004660
%V 53
%W Horizon (IRD)
%X 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.
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