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. Epub 2014 Mar 18.

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.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antimalarials / chemical synthesis
  • Antimalarials / chemistry
  • Antimalarials / pharmacology*
  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Cell Proliferation / drug effects
  • Dose-Response Relationship, Drug
  • Drug Screening Assays, Antitumor
  • Electrochemical Techniques*
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry
  • Indoles / pharmacology*
  • MCF-7 Cells
  • Molecular Structure
  • Parasitic Sensitivity Tests
  • Plasmodium falciparum / drug effects*
  • Structure-Activity Relationship

Substances

  • Antimalarials
  • Antineoplastic Agents
  • Indoles