Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives

Francoise Nepveu; 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

doi:10.1021/jm901300d

Retour

Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives

Article de revue

Avec comité de lecture

Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives

Francoise Nepveu, Sothea Kim, Jeremie Boyer, Olivier Chatriant, Hany Ibrahim, Karine Reybier, Marie-Carmen Monje, Severine Chevalley, Pierre Perio, Barbora H. Lajoie, …

Journal of medicinal chemistry, Vol.53(2), pp.699-714

28/01/2010

DOI: https://doi.org/10.1021/jm901300d

PMID: 20014857

Résumé

Chemistry, Medicinal

Life Sciences & Biomedicine

Pharmacology & Pharmacy

Science & Technology

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.

Indicateurs

1 Consultations de la notice

Détails

Titre: Synthesis and Antiplasmodial Activity of New Indolone N-Oxide Derivatives
Créateurs - sans rôle: Francoise Nepveu - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Sothea Kim - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Jeremie Boyer - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Olivier Chatriant - IDEALP PHARMA, F-69603 Villeurbanne, France
Hany Ibrahim - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Karine Reybier - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Marie-Carmen Monje - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Severine Chevalley - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Pierre Perio - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Barbora H. Lajoie - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Jalloul Bouajila - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Eric Deharo - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Michel Sauvain - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Rachida Tahar - Org Cooperat & Coordinat Lutte Contre Endemies Afr, Yaounde, Cameroon
Leonardo Basco - Org Cooperat & Coordinat Lutte Contre Endemies Afr, Yaounde, Cameroon
Antonella Pantaleo - Univ Turin, Sch Med, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy
Francesco Turini - Univ Turin, Sch Med, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy
Paolo Arese - Univ Turin, Sch Med, Dipartimento Genet Biol & Biochim, I-10126 Turin, Italy
Alexis Valentin - Univ Toulouse, UPS, UMR 152, Lab Pharmacochim Subst Nat & Pharmacophores Redox, F-31062 Toulouse 9, France
Eloise Thompson - LSHTM, London C1E 7HT, England
Livia Vivas - LSHTM, London C1E 7HT, England
Serge Petit - IDEALP PHARMA, F-69603 Villeurbanne, France
Jean-Pierre Nallet - IDEALP PHARMA, F-69603 Villeurbanne, France
Détails de publication: Journal of medicinal chemistry, Vol.53(2), pp.699-714
Éditeur: Amer Chemical Soc
Nombre de pages: 16
Note de subvention: Fondation Pierre Fabre FP6-2004-LSH-2004-2.3.0-7 / European Union; European Union (EU)
Identifiants: 99147927609311
Unité académique: Maladies Infectieuses et Vecteurs : Ecologie, Génétique, Evolution et Contrôle - MIVEGEC
Langue: English
Type de ressource: Journal article