Arylthioindoles, potent inhibitors of tubulin polymerization

J Med Chem. 2004 Dec 2;47(25):6120-3. doi: 10.1021/jm049360d.

Abstract

Several arylthioindoles had excellent activity as inhibitors both of tubulin polymerization and of the growth of MCF-7 human breast carcinoma cells. Methyl 3-[(3,4,5-trimethoxyphenyl)thio]-5-methoxy-1H-indole-2-carboxylate (21), the most potent derivative, showed IC(50) = 2.0 microM, 1.6 times more active than colchicine and about as active as combretastatin A-4 (CSA4). Compound 21 inhibited the growth of the MCF-7 cells at IC(50) = 13 nM. Colchicine and CSA4 had 13 nM and 17 nM IC(50) values, respectively, with these cells.

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / chemistry
  • Antineoplastic Agents / pharmacology
  • Biopolymers
  • Cell Line, Tumor
  • Crystallography, X-Ray
  • Depression, Chemical
  • Drug Screening Assays, Antitumor
  • Humans
  • Indoles / chemical synthesis*
  • Indoles / chemistry
  • Indoles / pharmacology
  • Models, Molecular
  • Sulfides / chemical synthesis*
  • Sulfides / chemistry
  • Sulfides / pharmacology
  • Tubulin / chemistry*
  • Tubulin Modulators*

Substances

  • Antineoplastic Agents
  • Biopolymers
  • Indoles
  • Sulfides
  • Tubulin
  • Tubulin Modulators