2-Aryl-3H-indol-3-ones: synthesis, electrochemical behaviour and antiplasmodial activities

  • Eur J Med Chem. 2014 May 6:78:269-74. doi: 10.1016/j.ejmech.2014.03.059.
Ennaji Najahi  1 ,  Alexis Valentin  2 ,  Paul-Louis Fabre  2 ,  Karine Reybier  2 ,  Françoise Nepveu  2
Affiliations
  • 1. Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France. Electronic address: [email protected].
  • 2. Université de Toulouse III, UPS, PHARMA-DEV, UMR 152, 118 Route de Narbonne, F-31062 Toulouse Cedex 9, France; IRD, UMR 152, F-31062 Toulouse Cedex 9, France.
PMID: 24686013 DOI: 10.1016/j.ejmech.2014.03.059
Abstract

The synthesis of indolone derivatives and their antiplasmodial activity in vitro against Plasmodium falciparum at the blood stage are described. The 2-aryl-3H-indol-3-ones were synthesized via deoxygenation of indolone-N-oxides. Electrochemical behaviour, antiplasmodial activity and cytotoxicity on human tumor cell lines were compared to those of indolone-N-oxides. The antiplasmodial IC50 (concentrations at 50% inhibition) of these compounds ranged between 49 and 1327 nM. Among them, the 2-(4-dimethylaminophenyl)-5-methoxy-indol-3-one, 7, had the best antiplasmodial activity in vitro (IC50 = 49 nM; FcB1 strain) and selectivity index (SI (CC50 MCF7/IC50 FcB1) = 423.4). Thus, the hits identified in this deoxygenated series correspond to their structural homologs in the N-oxide series with comparable electrochemical behaviour at the nitrogen-carbon double bond.

Keywords
2-Aryl-3H-indol-3-ones; Antiplasmodial activity; Deoxygenation; Electrochemical behaviour; Indolone-N-oxides.