Synthesis and biological evaluation of 1-methyl-2-(3',4',5'-trimethoxybenzoyl)-3-aminoindoles as a new class of antimitotic agents and tubulin inhibitors

J Med Chem. 2008 Mar 13;51(5):1464-8. doi: 10.1021/jm7011547. Epub 2008 Feb 9.

Abstract

The 2-(3,4,5-trimethoxybenzoyl)-2-aminoindole nucleus was used as the fundamental structure for the synthesis of compounds modified with respect to positions C-4 to C-7 with different moieties (chloro, methyl, or methoxy). Additional structural variations concerned the indole nitrogen, which was alkylated with small alkyl groups such as methyl or ethyl. We have identified 1-methyl-2-(3,4,5-trimethoxybenzoyl)-3-amino-7-methoxyindole as a new highly potent antiproliferative agent that targets tubulin at the colchicine binding site and leads to apoptotic cell death.

MeSH terms

  • Animals
  • Antimitotic Agents / chemical synthesis*
  • Antimitotic Agents / chemistry
  • Antimitotic Agents / pharmacology
  • Binding Sites
  • Biopolymers
  • Cell Line, Tumor
  • Colchicine / chemistry
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Mice
  • Models, Molecular
  • Protein Binding
  • Structure-Activity Relationship
  • Tubulin / chemistry
  • Tubulin Modulators / chemical synthesis
  • Tubulin Modulators / chemistry
  • Tubulin Modulators / pharmacology

Substances

  • 1-methyl-2-(3',4',5'-trimethoxybenozyl)-3-amino-7-methoxyindole
  • Antimitotic Agents
  • Biopolymers
  • Indoles
  • Tubulin
  • Tubulin Modulators
  • Colchicine