Document Report Card

ID: ALA1156797

Journal: J Med Chem

Title: Synthesis and antiplasmodial activity of new indolone N-oxide derivatives.

Authors: Nepveu F, Kim S, Boyer J, Chatriant O, Ibrahim H, Reybier K, Monje MC, Chevalley S, Perio P, Lajoie BH, Bouajila J, Deharo E, Sauvain M, Tahar R, Basco L, Pantaleo A, Turini F, Arese P, Valentin A, Thompson E, Vivas L, Petit S, Nallet JP.

Abstract: 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.), as well as for cytotoxic concentration (CC(50)) 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 (CC(50) MCF7/IC(50) FcB1: 14623; CC(50) KB/IC(50) 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.

CiteXplore: 20014857

DOI: 10.1021/jm901300d