Synthesis and Antiplasmodial Activity of New Indolone <i>N</i>-Oxide Derivatives - Pharmacochimie et Biologie pour le Développement Access content directly
Journal Articles Journal of Medicinal Chemistry Year : 2009

Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives

Sothea Kim
  • Function : Author
Jeremie Boyer
  • Function : Author
Olivier Chatriant
  • Function : Author
Hany Ibrahim
  • Function : Author
Karine Reybier
  • Function : Author
Marie-Carmen Monje
  • Function : Author
Severine Chevalley
  • Function : Author
Pierre Perio
  • Function : Author
Barbora H Lajoie
  • Function : Author
Jalloul Bouajila
  • Function : Author
Eric Deharo
  • Function : Author
  • PersonId : 1073326
Michel Sauvain
  • Function : Author
Rachida Tahar
  • Function : Author
Leonardo Basco
  • Function : Author
Antonella Pantaleo
  • Function : Author
Francesco Turini
  • Function : Author
Paolo Arese
  • Function : Author
Alexis Valentin
  • Function : Author
Eloise Thompson
  • Function : Author
Livia Vivas
  • Function : Author
Serge Petit
  • Function : Author
Jean-Pierre Nallet
  • Function : Author

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 pyri- methamine cross-resistant (K1) strains of Plasmodium falciparum (P.f.), as 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 antiplas- modial activity against Plasmodium berghei, 62% inhibition of the parasitaemia at 30 mg/kg/day.
Fichier principal
Vignette du fichier
Nepveu_2009.pdf (1.26 Mo) Télécharger le fichier
Origin : Files produced by the author(s)

Dates and versions

hal-04492867 , version 1 (06-03-2024)

Identifiers

Cite

Françoise Nepveu, Sothea Kim, Jeremie Boyer, Olivier Chatriant, Hany Ibrahim, et al.. Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives. Journal of Medicinal Chemistry, 2009, 53, pp.699 - 714. ⟨10.1021/jm901300d⟩. ⟨hal-04492867⟩
30 View
4 Download

Altmetric

Share

Gmail Facebook X LinkedIn More