3-substitued indoles: one-pot synthesis and evaluation of anticancer and Src kinase inhibitory activities

Bioorg Med Chem Lett. 2011 Jun 15;21(12):3511-4. doi: 10.1016/j.bmcl.2011.05.010. Epub 2011 May 7.

Abstract

An efficient and economical method was developed for the synthesis of 3-substituted indoles by one-pot three-component coupling reaction of a substituted or unsubstituted benzaldehyde, N-methylaniline, and indole or N-methylindole using Yb(OTf)(3)-SiO(2) as a catalyst. All the synthesized compounds were evaluated for inhibition of cell proliferation of human colon carcinoma (HT-29), human ovarian adenocarcinoma (SK-OV-3), and c-Src kinase activity. The 4-methylphenyl (4o and 4p) and 4-methoxyphenyl (4q) indole derivatives inhibited the cell proliferation of SK-OV-3 and HT-29 cells by 70-77% at a concentration of 50 μM. The unsubstituted phenyl (4d) and 3-nitrophenyl (4l) derivatives showed the inhibition of c-Src kinase with IC(50) values of 50.6 and 58.3 μM, respectively.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Aniline Compounds / chemistry
  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology*
  • Benzaldehydes / chemistry
  • Binding Sites
  • Catalysis
  • Cell Proliferation / drug effects
  • HT29 Cells
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / pharmacology*
  • Models, Molecular
  • Molecular Structure
  • Silicon Dioxide / chemistry
  • Ytterbium / chemistry
  • src-Family Kinases / antagonists & inhibitors*

Substances

  • Aniline Compounds
  • Antineoplastic Agents
  • Benzaldehydes
  • Indoles
  • Silicon Dioxide
  • src-Family Kinases
  • Ytterbium
  • benzaldehyde
  • methylaniline