Discovery of 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate as a potential antiproliferative agent by inhibiting histone deacetylase

Bioorg Med Chem. 2010 Dec 15;18(24):8457-62. doi: 10.1016/j.bmc.2010.10.049. Epub 2010 Oct 25.

Abstract

Twenty-one benzotriazoles (3-16 and 18-24) were synthesized and half of them (5, 8-16, 20, and 21) were reported for the first time. Their antiproliferative activities against three human cancer cells were assayed. It revealed that 1H-benzo[d][1,2,3]triazol-1-yl 3,4,5-trimethoxybenzoate (9) showed considerable activity against three human cancer cell lines with the half maximal inhibitory concentration (IC(50)) values of 1.2-2.4 nM, which were close to the value of the positive control, doxorubicin. Further investigation indicated compound 9 was a potential histone deacetylase inhibitor (IC(50)=9.4 μM) and its binding mode was simulated using docking method.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Antineoplastic Agents / chemical synthesis*
  • Antineoplastic Agents / pharmacology
  • Benzoates / chemical synthesis*
  • Benzoates / pharmacology
  • Binding Sites
  • Cell Line, Tumor
  • Doxorubicin / pharmacology
  • Drug Discovery*
  • Histone Deacetylase Inhibitors / chemical synthesis*
  • Histone Deacetylase Inhibitors / pharmacology
  • Humans
  • Inhibitory Concentration 50
  • Protein Binding
  • Structure-Activity Relationship
  • Triazoles / chemical synthesis
  • Triazoles / pharmacology

Substances

  • Antineoplastic Agents
  • Benzoates
  • Histone Deacetylase Inhibitors
  • Triazoles
  • Doxorubicin