| Literature DB >> 20014857 |
Françoise Nepveu1, Sothea Kim, Jeremie Boyer, Olivier Chatriant, Hany Ibrahim, Karine Reybier, Marie-Carmen Monje, Severine Chevalley, Pierre Perio, Barbora H Lajoie, Jalloul Bouajila, Eric Deharo, Michel Sauvain, Rachida Tahar, Leonardo Basco, Antonella Pantaleo, Francesco Turini, Paolo Arese, Alexis Valentin, Eloise Thompson, Livia Vivas, Serge Petit, Jean-Pierre Nallet.
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.Entities:
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Year: 2010 PMID： 20014857 DOI： 10.1021/jm901300d
Source DB: PubMed Journal: J Med Chem ISSN： 0022-2623 Impact factor: 7.446