1-Toluene-sulfonyl-3-[(3'-hydroxy-5'-substituted)-gamma-butyrolactone]-indoles: synthesis, COX-2 inhibition and anti-cancer activities

Bioorg Med Chem Lett. 2008 Jan 1;18(1):85-9. doi: 10.1016/j.bmcl.2007.11.010. Epub 2007 Nov 6.

Abstract

Indoles carrying a cyclic ester (gamma-butyrolactone) at C-3 position have been synthesized by the allylation of 3-indoleglyoxylate followed by iodocyclisation and the nucleophilic replacement of the iodo-group. Screening of these molecules for COX-2 inhibition and anti-cancer activities has identified compounds 10 and 11 as highly potent and selective for COX-2 as well as showing remarkable anti-cancer activities (better than that of indomethacin).

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • 4-Butyrolactone / analogs & derivatives*
  • 4-Butyrolactone / chemical synthesis
  • 4-Butyrolactone / pharmacology
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Binding Sites
  • Cell Line, Tumor
  • Cyclooxygenase 2 / chemistry
  • Cyclooxygenase 2 / metabolism
  • Cyclooxygenase 2 Inhibitors / chemical synthesis*
  • Cyclooxygenase 2 Inhibitors / chemistry
  • Cyclooxygenase 2 Inhibitors / pharmacology*
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology*
  • Models, Molecular
  • Tosyl Compounds / chemical synthesis
  • Tosyl Compounds / chemistry
  • Tosyl Compounds / pharmacology

Substances

  • Antineoplastic Agents
  • Cyclooxygenase 2 Inhibitors
  • Indoles
  • Tosyl Compounds
  • Cyclooxygenase 2
  • 4-Butyrolactone