Design, synthesis and pro-apoptotic antitumour properties of indole-based 3,5-disubstituted oxadiazoles

Eur J Med Chem. 2010 Oct;45(10):4523-30. doi: 10.1016/j.ejmech.2010.07.012. Epub 2010 Jul 21.

Abstract

A series of new indole-based 3,5-disubstituted 1,2,4-oxadiazoles has been designed and synthesised as potential pro-apoptotic antitumour agents, via the base-catalysed condensation reaction between substituted amidoximes and indole esters. Evaluation of antiproliferative activity against the human cancer cell lines COLO 320 (colorectal) and MIA PACA-2 (pancreatic) revealed IC(50) values in the low micromolar range. Selected compounds were able to trigger apoptosis in sensitive cell lines, for example via activation of caspase-3/7, demonstrating that indole-based oxadiazoles possess in vitro antitumour and pro-apoptotic activity.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis
  • Antineoplastic Agents / chemistry*
  • Antineoplastic Agents / pharmacology*
  • Apoptosis / drug effects*
  • Cell Line
  • Cell Line, Tumor
  • Cell Survival / drug effects
  • Colorectal Neoplasms / drug therapy
  • Drug Design
  • Humans
  • Indoles / chemical synthesis
  • Indoles / chemistry*
  • Indoles / pharmacology*
  • Myocytes, Cardiac / cytology
  • Myocytes, Cardiac / drug effects
  • Oxadiazoles / chemical synthesis
  • Oxadiazoles / chemistry*
  • Oxadiazoles / pharmacology*
  • Pancreatic Neoplasms / drug therapy
  • Structure-Activity Relationship

Substances

  • Antineoplastic Agents
  • Indoles
  • Oxadiazoles